CANDIDA Y CANDIDIASIS.enfermedades del aparato genital

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Candida
and Candidiasis
s e c o n d e d i t i o n

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Candida
and Candidiasis
s e c o n d e d i t i o n
e d i t e d b y
Richard A. Calderone
Georgetown University Medical Center, Washington, DC
Cornelius J. Clancy
Department of Medicine, Infectious Diseases Division,
University of Pittsburgh, Pittsburgh, PA
W A S H I N G T O N , D C

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Cover: Candida albicans (red) and Staphylococcus aureus (green) biofilm stained with species-specific pep-
tide nucleic acid (PNA)-FISH probes, demonstrating extensive adherence of S. aureus to the C. albicans
hyphae. Courtesy Mary Ann Jabra-Rizk, University of Maryland, Baltimore.
Copyright © 2012 by ASM Press. ASM Press is a registered trademark of the American Society for
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Library of Congress Cataloging-in-Publication Data
Candida and candidiasis / edited by Richard A. Calderone, Cornelius J. Clancy. — 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-55581-539-4
1. Candidiasis. 2. Candida. I. Calderone, Richard A., 1942- II. Clancy, Cornelius J.
[DNLM: 1. Candida. 2. Candidiasis. QW 180.5.D38]
QR201.C27C365 2012
616.9'693—dc23
2011025353
E-Book ISBN 978-1-55581-717-6
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
Address editorial correspondence to: ASM Press, 1752 N St., N.W., Washington, DC
20036-2904, USA.
Send orders to: ASM Press, P.O. Box 605, Herndon, VA 20172, USA.
Phone: 800-546-2416; 703-661-1593. Fax: 703-661-1501.
E-mail: books@asmusa.org
Online: http://estore.asm.org

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v
Contents
Contributors / vii
Preface / xi
1 Candida: What Should Clinicians and
Scientists Be Talking About? / 1
BRAD SPELLBERG, KIEREN A. MARR,
AND SCOTT G. FILLER
SECTION I
THE ORGANISMS, THEIR GENOMICS, AND
VARIABILITY / 9
2 An Introduction to the Medically Important
Candida Species / 11
GARY MORAN, DAVID COLEMAN, AND DEREK
SULLIVAN
3 Comparative Genomics of Candida
Species / 27
GERALDINE BUTLER
4 The Genetic Code of the Candida CTG
Clade / 45
ANA CATARINA GOMES, GABRIELA R. MOURA,
AND MANUEL A. S. SANTOS
5 Genome Instability and DNA Repair / 57
GERMÁN LARRIBA AND RICHARD A. CALDERONE
6 Switching and Mating / 75
DAVID R. SOLL
7 Detection and Clinical Signiﬁcance
of Variability among Candida Isolates / 91
LOIS L. HOYER
8 Cell Cycle and Growth Control in Candida
Species / 101
CHERYL A. GALE AND JUDITH BERMAN
SECTION II
HOST-PATHOGEN INTERACTIONS
(THE HOST) / 125
9 Immunology of Invasive Candidiasis / 127
LUIGINA ROMANI
10 Mucosal Immunity to Candida
albicans / 137
PAUL L. FIDEL, JR., AND MAIRI C. NOVERR
11 Innate Immunity to Candida
Infections / 155
MIHAI G. NETEA AND NEIL A. R. GOW
12 Vaccines and Passive Immunity against
Candidiasis / 171
BRAD SPELLBERG, YUE FU, AND ASHRAF S. IBRAHIM
13 Salivary Histatins: Structure, Function,
and Mechanisms of Antifungal Activity / 185
WOON SIK JANG AND MIRA EDGERTON
SECTION III
HOST-PATHOGEN INTERACTIONS
(THE PATHOGEN) / 195
14 The Cell Wall: Glycoproteins, Remodeling,
and Regulation / 197
CAROL MUNRO AND MATHIAS L. RICHARD

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vi CONTENTS
15 Stress Responses in Candida / 225
ALISTAIR J. P. BROWN, KEN HAYNES, NEIL A. R. GOW,
AND JANET QUINN
16 Adhesins in Opportunistic Fungal
Pathogens / 243
REBECCA ZORDAN AND BRENDAN CORMACK
17 Encounters with Mammalian Cells:
Survival Strategies of Candida Species / 261
SLAVENA VYLKOVA AND MICHAEL C. LORENZ
18 Gene Expression during the Distinct
Stages of Candidiasis / 283
DUNCAN WILSON, FRANCOIS MAYER,
AND BERNHARD HUBE
19 Bioﬁlm Formation in Candida
albicans / 299
JONATHAN SEWELL FINKEL AND
AARON P. MITCHELL
20 Candida spp. in Microbial Populations
and Communities: Molecular Interactions
and Biological Importance / 317
AMY E. PIISPANEN AND DEBORAH A. HOGAN
21 Back to the Future: Candida Mitochondria
and Energetics / 331
DEEPU ALEX, RICHARD CALDERONE,
AND DONGMEI LI
SECTION IV
ANTIFUNGAL DRUGS, DRUG RESISTANCE,
AND DISCOVERY / 343
22 Antifungals: Drug Class, Mechanisms of
Action, Pharmacokinetics/Pharmacodynamics,
Drug-Drug Interactions, Toxicity, and Clinical
Use / 345
JENIEL E. NETT AND DAVID R. ANDES
23 The Impact of Antifungal Drug Resistance
in the Clinic / 373
RUSSELL E. LEWIS AND DIMITRIOS P.
KONTOYIANNIS
24 Insights in Antifungal Drug
Discovery / 387
FRANÇOISE GAY-ANDRIEU, JARED MAY, DONGMEI
LI, NUO SUN, HUI CHEN, RICHARD CALDERONE,
AND DEEPU ALEX
25 Multidrug Resistance Transcriptional
Regulatory Networks in Candida / 403
P. DAVID ROGERS AND KATHERINE S. BARKER
SECTION V
CANDIDIASIS, EVOLVING DIAGNOSTICS,
AND TREATMENT PARADIGMS / 417
26 Mucosal Candidiasis / 419
SANJAY G. REVANKAR AND JACK D. SOBEL
27 Systemic Candidiasis: Candidemia and
Deep-Organ Infections / 429
CORNELIUS J. CLANCY AND M. HONG NGUYEN
28 New Developments in Diagnostics and
Management of Invasive Candidiasis / 443
SUJATHA KRISHNAN AND LUIS OSTROSKY-
ZEICHNER
29 The Epidemiology of Invasive
Candidiasis / 449
MICHAEL A. PFALLER AND DANIEL J. DIEKEMA
SECTION VI
COOL TOOLS FOR RESEARCH / 481
30 Cool Tools 1: Development and
Application of a Candida albicans
Two-Hybrid System / 483
BRAM STYNEN, PATRICK VAN DIJCK,
AND HÉLÈNE TOURNU
31 Cool Tools 2: Development of a Candida
albicans Cell Surface Protein Microarray / 489
A. BRIAN MOCHON
32 Cool Tools 3: Large-Scale Genetic
Interaction Screening in Candida
albicans / 497
YEISSA CHABRIER-ROSELLÓ, ANUJ KUMAR,
AND DAMIAN KRYSAN
33 Cool Tools 4: Imaging Candida Infections
in the Live Host / 501
SOUMYA MITRA, THOMAS H. FOSTER,
AND MELANIE WELLINGTON
34 Cool Tools 5: The Candida albicans
ORFeome Project / 505
MÉLANIE LEGRAND, CAROL MUNRO, AND
CHRISTOPHE D’ENFERT
Index / 511

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vii
Contributors
DEEPU ALEX
Georgetown University Medical Center, Washington,
DC 20057
DAVID R. ANDES
Department of Medicine, Medical Microbiology and
Immunology, University of Wisconsin School of Medicine
and Public Health, Madison, WI 53792
KATHERINE S. BARKER
Department of Clinical Pharmacy, College of Pharmacy,
University of Tennessee Health Science Center, Children’s
Foundation Research Center, Le Bonheur Children’s Hospital,
Memphis, TN 38163
JUDITH BERMAN
Department of Genetics, Cell Biology and Development
and Department of Microbiology, University of Minnesota,
Minneapolis, MN 55455
ALISTAIR J. P. BROWN
School of Medical Sciences, University of Aberdeen, Institute
of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD,
United Kingdom
GERALDINE BUTLER
School of Biomolecular and Biomedical Science,
Conway Institute, University College Dublin, Belﬁeld,
Dublin 4, Ireland
RICHARD A. CALDERONE
Department of Microbiology and Epidemiology, Medical
School, Georgetown University, Washington, DC 20057
YEISSA CHABRIER-ROSELLÓ
Department of Pediatrics, University of Rochester, School
of Medicine and Dentistry, Box 850, 601 Elmwood Ave.,
Rochester, NY 14642
HUI CHEN
DC 20057
CORNELIUS J. CLANCY
Department of Medicine, University of Pittsburgh, Pittsburgh,
PA 15261
DAVID COLEMAN
Microbiology Research Unit, Division of Oral Biosciences,
Dublin Dental School & Hospital, Trinity College Dublin,
University of Dublin, Dublin 2, Ireland
BRENDAN CORMACK
Department of Molecular Biology and Genetics, Johns
Hopkins University School of Medicine, Baltimore,
MD 21205
CHRISTOPHE D’ENFERT
Institut Pasteur, Unité Biologie et Pathogénicité Fongiques,
Département Génomes et Génétique, and INRA, USC2019,
F-75015 Paris, France
DANIEL J. DIEKEMA
Departments of Pathology and Medicine, University of Iowa
Carver College of Medicine, Iowa City, IA 52242
MIRA EDGERTON
Department of Oral Biology, School of Dental Medicine, State
University of New York at Buffalo, Buffalo, NY 14214
PAUL L. FIDEL, JR.
Department of Oral and Craniofacial Biology, Louisiana State
University Health Sciences Center, School of Dentistry,
New Orleans, LA 70119
SCOTT G. FILLER
David Geffen School of Medicine at the University of
California Los Angeles (UCLA), and Division of Infectious
Diseases, Los Angeles Biomedical Research Institute,
Harbor-UCLA Medical Center, Torrance, CA 90502
JONATHAN SEWELL FINKEL
Department of Biological Sciences, Carnegie Mellon
University, 4400 Fifth Avenue, Pittsburgh, PA 15213

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viii CONTRIBUTORS
THOMAS H. FOSTER
Department of Imaging Sciences, University of Rochester
Medical Center, 601 Elmwood Ave., Box 648, Rochester,
NY 14642
YUE FU
David Geffen School of Medicine at UCLA, and Division
of Infectious Diseases, Los Angeles Biomedical Research
Institute, Harbor-UCLA Medical Center, Torrance,
CA 90502
CHERYL A. GALE
Department of Pediatrics and Department of Genetics,
Cell Biology and Development, University of Minnesota,
Minneapolis, MN 55455
FRANÇOISE GAY-ANDRIEU
DC 20057, and Nantes Atlantique Universities, EA1155-
IICiMed, Nantes, France
ANA CATARINA GOMES
Genomics Unit, Biocant, BiocantPark–Parque Tecnologico de
Cantanhede, 3060-197 Cantanhede, Portugal
NEIL A. R. GOW
School of Medical Sciences, University of Aberdeen, Institute
of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD,
United Kingdom
KEN HAYNES
School of Biosciences, University of Exeter, Exeter, EX4 4QD,
United Kingdom
DEBORAH A. HOGAN
Department of Microbiology and Immunology, Dartmouth
Medical School, Hanover, NH 03755
LOIS L. HOYER
Department of Pathobiology, University of Illinois at
Urbana-Champaign, Urbana, IL 61802
BERNHARD HUBE
Department of Microbial Pathogenicity Mechanisms, Leibniz
Institute for Natural Product Research and Infection Biology,
Hans Knoell Institute Jena (HKI), Beutenbergstrasse 11a,
D-07745 Jena, Germany
ASHRAF S. IBRAHIM
David Geffen School of Medicine at UCLA, and Division
of Infectious Diseases, Los Angeles Biomedical Research
Institute, Harbor-UCLA Medical Center, Torrance,
CA 90502
WOON SIK JANG
Department of Oral Biology, School of Dental Medicine, State
University of New York at Buffalo, Buffalo, NY 14214
DIMITRIOS P. KONTOYIANNIS
University of Houston College of Pharmacy and
University of Texas M. D. Anderson Cancer Center,
Houston, TX 77030
SUJATHA KRISHNAN
Division of Infectious Diseases, University of Texas Medical
School at Houston, Houston, TX 77030
DAMIAN KRYSAN
Departments of Pediatrics and Microbiology/Immunology,
University of Rochester, School of Medicine and Dentistry,
Box 850, 601 Elmwood Ave., Rochester, NY 14642
ANUJ KUMAR
Department of Molecular, Cellular, and Developmental
Biology, Life Sciences Institute, 210 Washtenaw Avenue, Ann
Arbor, MI 48109
GERMÁN LARRIBA
Área Microbiología, Ediﬁcio Biológicas, F. Ciencias,
Universidad de Extremadura, 06006 Badajoz, Spain
MÉLANIE LEGRAND
Institut Pasteur, Unité Biologie et Pathogénicité Fongiques,
Département Génomes et Génétique, and INRA, USC2019,
F-75015 Paris, France
RUSSELL E. LEWIS
University of Houston College of Pharmacy and University of
Texas M. D. Anderson Cancer Center, Houston,
TX 77030
DONGMEI LI
DC 20057
MICHAEL C. LORENZ
Department of Microbiology and Molecular Genetics, The
University of Texas Health Science Center, 6431 Fannin St.,
Houston, TX 77030
KIEREN A. MARR
Division of Infectious Diseases, Johns Hopkins University
School of Medicine, Baltimore, MD 21205
JARED MAY
DC 20057
FRANCOIS MAYER
AARON P. MITCHELL
Department of Biological Sciences, Carnegie Mellon
University, 4400 Fifth Avenue, Pittsburgh, PA 15213
SOUMYA MITRA
Department of Imaging Sciences, University of Rochester
Medical Center, 601 Elmwood Ave., Box 648, Rochester,
NY 14642
A. BRIAN MOCHON
Department of Pathology and Laboratory Medicine, David
Geffen School of Medicine at UCLA, 10833 Le Conte Ave.,
Brentwood Annex, Los Angeles, CA 90095-1732
GARY MORAN

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Contributors ix
GABRIELA R. MOURA
Department of Biology and CESAM, University of Aveiro,
Campus de Santiago, 3810-193 Aveiro, Portugal
CAROL MUNRO
Aberdeen Fungal Group, University of Aberdeen, School of
Medical Sciences, Institute of Medical Sciences, Aberdeen,
AB25 2ZD, United Kingdom
MIHAI G. NETEA
Department of Medicine and Nijmegen University Centre for
Infectious Diseases, Radboud University Nijmegen Medical
Centre, Nijmegen, The Netherlands
JENIEL E. NETT
Department of Medicine, Medical Microbiology and
Immunology, University of Wisconsin School of Medicine
and Public Health, Madison, WI 53792
M. HONG NGUYEN
Department of Medicine, University of Pittsburgh, Pittsburgh,
PA 15261
MAIRI C. NOVERR
Department of Oral and Craniofacial Biology, Louisiana State
University Health Sciences Center, School of Dentistry, New
Orleans, LA 70119
LUIS OSTROSKY-ZEICHNER
Division of Infectious Diseases, University of Texas Medical
School at Houston, Houston, TX 77030
MICHAEL A. PFALLER
Department of Pathology, University of Iowa Carver College
of Medicine, and Department of Epidemiology, University of
Iowa College of Public Health, Iowa City, IA 52242
AMY E. PIISPANEN
Department of Microbiology and Immunology, Dartmouth
Medical School, Hanover, NH 03755
JANET QUINN
Institute for Cell and Molecular Biosciences, Newcastle
University, Newcastle upon Tyne, NE2 4HH, United
Kingdom
SANJAY G. REVANKAR
Division of Infectious Diseases, Wayne State University
School of Medicine, Detroit, MI 48201
MATHIAS L. RICHARD
MICrobiologie de l’ALImentation au service de la Santé,
Equipe “Virulence et Infection Fongique,” INRA UMR1319
AgroParisTech, 78850 Thiverval Grignon, France
P. DAVID ROGERS
Department of Clinical Pharmacy, College of Pharmacy,
University of Tennessee Health Science Center, Children’s
Foundation Research Center, Le Bonheur Children’s Hospital,
Memphis, TN 38163
LUIGINA ROMANI
Microbiology Section, Department of Experimental Medicine
and Biochemical Sciences, University of Perugia, Via del
Giochetto, 06122 Perugia, Italy
MANUEL A. S. SANTOS
Department of Biology and CESAM, University of Aveiro,
Campus de Santiago, 3810-193 Aveiro, Portugal
JACK D. SOBEL
Division of Infectious Diseases, Wayne State University
School of Medicine, Detroit, MI 48201
DAVID R. SOLL
Department of Biology, The University of Iowa, Iowa
City, IA 52242
BRAD SPELLBERG
Division of General Internal Medicine, Los Angeles
Biomedical Research Institute at Harbor-University of
California Los Angeles (UCLA) Medical Center,
and David Geffen School of Medicine at UCLA, Torrance,
CA 90502
BRAM STYNEN
VIB Department of Molecular Microbiology, K.U. Leuven
Laboratory of Molecular Cell Biology, Institute of Botany and
Microbiology, Kasteelpark Arenberg 31, Postbus 2438, B-3001
Leuven, Belgium
DEREK SULLIVAN
NUO SUN
DC 20057
HÉLÈNE TOURNU
Leuven, Belgium
PATRICK VAN DIJCK
Leuven, Belgium
SLAVENA VYLKOVA
Department of Microbiology and Molecular Genetics, The
University of Texas Health Science Center, 6431 Fannin St.,
Houston, TX 77030
MELANIE WELLINGTON
Department of Pediatrics, University of Rochester Medical
Center, 601 Elmwood Ave., Box 690, Rochester, NY 14642
DUNCAN WILSON
REBECCA ZORDAN
Department of Molecular Biology and Genetics, Johns
Hopkins University School of Medicine, Baltimore,
MD 21205

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xi
Preface
Over the past three decades, as one of the editors himself
has witnessed, the experimental approaches and desired
outcomes in the study of Candida spp. and the infections
they cause naturally have changed. The overwhelming focus
now is in molecular biology at a number of levels of research,
such as genome comparisons and assessing virulence factors
and host responses, as well as the promise of translational
research into new antifungal drug discovery, diagnostics,
and vaccines. The Candida community has been fortunate
to witness the sharing of mutant libraries, strains, tech-
niques, vectors, and probes; collaboration among laborato-
ries seems to be increasing, a development that will be
needed to solve the increasing complexity of research that
requires interdisciplinary and “systems biology” approaches.
Through genomics, we can now identify similarities and dif-
ferences among Candida species, other human pathogenic
and nonpathogenic fungi, and nonfungal species. “Omics”
studies and databases are especially useful in designing new
targets for drug discovery, but their application extends be-
yond this goal, to showing why pathogens are pathogens.
That knowledge is in many cases at our fingertips.
This is the fourth in a series of volumes on Candida and
candidiasis (candidosis) and the first that is coedited to re-
flect a more thorough treatise of human disease, treatment,
and expectations in health care delivery. Each of the pre-
ceding books emphasized different things. Candida and Can-
didosis (University Park Press, Baltimore, MD, 1979) and
Candida and Candidosis: a Review and Bibliography, 2nd Ed.
(Baillière Tindall, Oxford, U.K., 1988), both written by
Frank C. Odds, focused on the species that cause candidia-
sis, including their morphogenesis, virulence, and structure;
the first of these books included special emphasis on the
types of candidiasis. Dr. Odds gave us meaning and direc-
tion, a unification to address new problems that existed.
The third book, Candida and Candidiasis, edited by Richard
A. Calderone, was published in 2002 by ASM Press.
The present book, Candida and Candidiasis, 2nd Edition,
is a natural extension of the previous three. In this volume
are emphasized genomes and variability, host-pathogen in-
teractions, antifungal resistance and new drug discovery,
and evolving diagnostics. Variability among Candida species
is described with regard to genomes, molecular adaptation
to the external milieu whether in a host or in vitro, and
sexuality of Candida albicans; we have learned how variabil-
ity contributes to resistance to triazole drugs. Traditional
areas of interest remain. For example, research in morpho-
genesis and the cell cycle (and, ultimately, growth) has pro-
vided new heights of understanding. Major advances in im-
mune responses are also covered in this volume. Chapters
discuss vaccine candidates in the community and how host
responses may be useful in diagnosis of blood-borne candidi-
asis. Virulence attributes are now placed in the context of
gene families. While the cell wall is critically included, it is
represented more now as an entity that interacts with the
innate host system. Broad representation of specific pieces
of the cell is included, ultimately reflecting the current in-
terests among like scientists. Biofilms, either mixed-species
or monospecific, tell us much about the survival of the fun-
gus in the host.
Discovery has continued, and translational research is
moving toward attainable goals. But have we made a differ-
ence in increasing awareness of public health issues in can-
didiasis? An answer to that question is not easily discerned.
Candidiasis is the third most frequent hospital-acquired in-
fection. But who knows that fact, beyond the candidiasis
community? In reality, new drug discovery features little
more than remodeled old drugs. The search for that magic
bullet that can kill all 100+ fungal pathogens still survives,
at least partially, but this objective lacks sense and is not
part of the paradigm in antibacterial drug discovery.
We must lose the notion that we cannot do better. The
greatest risk for the next decade is that candidiasis research
will become lost in the current economic times, at least in
the United States. Emphasis on other important, nonfungal
pathogens has overwhelmed the goal of controlling candidi-
asis, cryptococcosis, aspergillosis, the endemic mycoses, and
dermatophytosis in public health. Solutions to this dilemma
are not easy. To a much broader extent, we in this field must
educate the public by choosing leaders among us, especially
physician-scientists, who can testify to the importance of
these diseases. These leaders should be called on to seize the
interest of “think tanks” and other groups that influence
policy makers. But also, each of us needs to remind our pro-
fessional societies, the major advocates of microbiology, that
this field demands equal attention with all the other patho-
genic microorganisms, whether in newsletters, public edu-
cation, or influence peddling.
Even within our discipline, we cannot keep up with ev-
erything. Both of us marveled at the outstanding research
presented at the most recent “Candida and Candidiasis”

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xii PREFACE
conference, held in Miami Beach, Florida, in March of
2010. That message should continue to be carried to the
public, in a language that conveys the importance of these
diseases. For this reason, just as the present volume offers
the most current information in this critical ﬁeld, new books
on Candida and candidiasis should continue to present new
discoveries and developments.
RICHARD A. CALDERONE
CORNELIUS J. CLANCY

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511
Index
A
a/a and α/α cells, in mating, 75–84
ABC transporters, in drug resistance, 66
Abdomen, candidiasis in, 433–434
Abscess, brain, 434
Accidental infections, versus opportunistic
infections, 1–2
Ace2 protein
in biofilm formation, 301, 306
in carbon metabolism, 335
in cell cycle, 117
Acetic acid, stress response to, 228–229
N-Acetylglucosamine
in chitin synthesis, 197
in switching, 81, 83
Acid stress response, 228–229
Acinetobacter baumannii, Candida albicans
interactions with, 319–320
Aco1 protein
in kidney lesions, 290
in liver lesions, 292
Acs1 protein, in kidney lesions, 290
Actin, in cell cycle, 106–107
Active immunization, 5, 175–178
Ada2 protein, in multidrug resistance, 410
Adaptive immunity
activation of, 156–157
in gastrointestinal candidiasis, 141
Adh proteins
in biofilm formation, 301, 307–308
in morphogenesis, 334
Adhesins, 243–259
in biofilms, 249–250, 303–304
in Candida albicans, 245–250
in Candida glabrata, 250–253
cell wall structure and, 243
for endothelial cell invasion, 289–290
evolution of, 254–255
functions of, 243
in Saccharomyces cerevisiae, 253–254
structure of, 243–254
types of, 270–272
Adhesion
Als protein family in, 31–32
cell-cell, in biofilm formation, 304–306
Adhesion molecules, in oropharyngeal can-
didiasis, 139
Afbgt1 protein, in cell wall, 199
Affirm test, for mucosal candidiasis, 424
Agglutinin-like sequence genes, 15–16,
30–32
Ahp1 protein, in histatin response, 190
AI-2 protein, in fungal-bacterial interac-
tions, 320
AIDS, see HIV/AIDS
AIRE gene, polymorphisms of, 161
Albaconazole, 396
Alkylation, reversal of, 62
O6Alkylguanine-DNA alkyltransferase II,
in DNA repair, 66
Als protein family, 31–32
adherence properties of, 245–247,
270–272
amyloid formation and, 246–247
in biofilm formation, 301, 304–305
Candida albicans, 15–88, 245–247
in cell wall, 206, 208, 210
in colonization, 286
in dissemination, 289–290
in invasion, 288
iron acquisition and, 246
regulation of, 247
strain variation due to, 94, 96
structures of, 200, 245–247
in vaccine development, 175–178
Alternative oxidase pathway, for respira-
tion, 331
Ambiguous-intermediate theory, of codon
reassignment, 46–48
Amino acids
formation of, in biofilm formation, 307
starvation of, 261
Aminocandin, 396
Amphotericin B
for candidemia, 431–432
for cardiovascular candidiasis, 434–435
for central nervous system candidiasis,
434
chemical structure of, 348
clinical uses of, 350–351
cochleate formulation of, 396
dosing of, 350
drug-drug interactions of, 350
for hepatosplenic candidiasis, 433
lipid formulations of, 346–348
mechanism of action of, 347
for mucosal candidiasis, 421
for osteomyelitis, 435
for peritonitis, 433–434
pharmacodynamics of, 347–348
pharmacokinetics of, 347, 350
resistance to, 310, 403
spectrum of activity of, 347, 349
toxicity of, 348, 350
Amphotericin B deoxycholate
advantages of, 346
disadvantages of, 346
for endophthalmitis, 433
fluconazole with, 3
Ams1 protein, in dissemination, 290
Amyloid formation, Als proteins and,
246–247
Aneuploidy
genetic instability and, 58–60
in strain variation, 94
Angular cheilitis, 12, 420
Anidulafungin, 358–360
advantages of, 346
dosing of, 351
spectrum of activity of, 349
susceptibility to, 465–466, 468
Animal models
for adhesion action, 2
Candida imaging in, 501–503
for disseminated candidiasis, 2, 4, 95–96
for gastrointestinal candidiasis, 141–142
for oropharyngeal candidiasis, 138
for vulvovaginal candidiasis, 143, 145
Animals, strain variation found in, 95
Annexin, in oropharyngeal candidiasis,
139
Anp1 protein, in DNA repair, 62
Antibiotics, vulvovaginal candidiasis due
to, 172, 422
Antifungal drugs, see also specific drug
classes (polyenes) and individual
drug names
for Candida albicans, 16
clinical characteristics of, 345

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512 INDEX
Antifungal drugs (continued)
discovery of
approaches to, 391
current developments in, 395–396
genomic approaches to, 394–395
global candidiasis incidence and,
387–388
myths about, 396–397
traditional approaches to, 391–394
treatment difficulties and, 388–391
for disseminated candidiasis, 3–5, 9
economic costs of, 390–391
historical overview of, 345
mitochondria as targets of, 335–336
pharmacokinetics of, 346–347
pharmacology of, 345
preemptive, 44
susceptibility to, see Drug resistance;
Susceptibility
Antigen(s), cell surface, protein microarray
for, 489–496
Antigen-presenting cells, in innate immu-
nity, 159
Antiglucan antibodies, for vaccines,
174–175
Anti-heat shock protein antibodies, for
vaccines, 175
Antimannan antibodies
as biomarkers, 445
for vaccines, 174
Antimicrobial peptides, in oropharyngeal
candidiasis, 140
Antimycin (complex III), 331–336
Antioxidants, 232–233
in stress response, 227–228, 264–267,
334–335
AP-1 family, in stress response, 233–234
Apoptosis
in immunity modulation, 270
of macrophages, 156
Apurinic/apyrimidinic sites, in DNA repair,
62
Arabidopsis thaliana, codon reassignment in,
46
Arf1 protein, in general stress response, 229
ARTEMIS Surveillance Program, 16,
453–454
Arthritis, septic, 435
Aspartyl proteases, in cell wall, 202
Aspergillus
azoles for, 354
echinocandins for, 360
flucytosine for, 352
Aspergillus flavus, azoles for, 354
Aspergillus fumigatus
antifungal drugs for, 349
azoles for, 354
carbohydrate-active enzymes of, 199
cell wall of, glycoproteins of, 211, 213
farnesol effects on, 323
histatin action against, 185
infections due to, health care costs of,
390
meiosis in, 34
Aspergillus glabrata, glycoproteins of, 214
Aspergillus nidulans
azoles for, 354
genetic instability in, 58
Aspergillus terreus, azoles for, 354
Atg proteins, in nutrient starvation, 268
ATP, in histatin action, 190
ATP-binding cassette transporters, in mul-
tidrug resistance, 404
Autophagy, 268
Awp proteins, adhesive properties of, 253
Azoles, 352–358; see also individual drugs
chemistry of, 354
monitoring of, 356
new, 396
resistance to
multidrug, 404–412
targeting mitochondria, 335–336
toxicity of, 357
B
B6.1 antibody, for vaccines, 174
B lymphocytes, in immune response,
156–157
Bacillus subtilis, codon reassignment in, 46
Bacteria, in polymicrobial populations, see
Microbial populations and
communities
Bacterial microbiota, in gastrointestinal
tract, 142
Bait proteins, in two-hybrid system,
483–487
BAL4815 (isavuconazole), 396
Bar1 protein, in mating, 80
Basal septin band, 108
Base excision repair, 62–63
Bcr1 protein
in biofilms, 249, 301, 304, 306
in cell wall, 198
BENr transporter, in multidrug resistance,
404
Benzoic acid, stress response to, 228–229
Beta glucan test, 3
Bifidobacterium, in gastrointestinal tract,
142
Bifidobacterium infantis, for candidiasis, 322
Big1 protein, in cell wall, 199
Biofilms, 85, 299–315
on abiotic surfaces, 317–318
adhesins in, 249–250
Als protein family in, 31–32
Candida albicans in, 299–315
Candida glabrata in, 252
Candida in, 145–146
drug resistance within, 309–310,
317–318
formation of, 323
Candida mating and, 309
cell-cell communication in, 308–309
early functions in, 303–304
genetic control of, 300–303
late functions in, 306–308
middle functions in, 304–306
overview of, 299–300
polymicrobial, 317–318
substrates containing, 299
in vulvovaginal candidiasis, 423
Biomarkers
for invasive candidiasis, 443–446
protein microarray analysis for, 489–496
Blastomyces dermatitidis
azoles for, 354
polyenes for, 347
Blood cultures, disadvantages of, 2–3
Bloodstream, organism spread and escape
by, 289–290
Bone infections, 435
Brain, candidiasis of, 434
Break-induced replication, 28, 60–61
Broad Institute database, 37
Bud proteins, in cell cycle, 106–107
Bud site selection, 104, 106
Burkholderia cenocepacia, Candida albicans
interactions with, 320
Burkholderia cepacia, Candida albicans inter-
actions with, 319–320
C
CaAda2 protein, in multidrug resistance,
410
Cables, in cell cycle, 106–107
CaCrm1 protein, in multidrug resistance,
410
CaCrz1 protein, in multidrug resistance,
410–411
Cadherins, in oropharyngeal candidiasis,
139
Cadmium, stress response to, 229
CaFcr proteins, in multidrug resistance, 411
Cag1 protein
in mating, 79, 84, 85
in reproduction, 75
Calcein, 187
Calcineurin
drug resistance and, 310
in multidrug resistance, 410–411
Calcium-binding proteins, in vulvovaginal
candidiasis, 145
CalFpg protein, n DNA repair, 62–63
Calprotectin, in oropharyngeal candidiasis,
140
CaMcm1 protein, in multidrug resistance,
409
Candida
imaging of, in animals, 501–503
number of species in, 11
phylogeny of, 27
stress responses in, 225–242
taxonomy of, 11
Candida africana, 92–93
Candida albicans, 14–16
adaptive immune response to, 156–157
adhesins of, 245–250, 270–272
adjuvant immunotherapy for, 162–163
antifungal susceptibility of, 16, 161–163,
349–350, 465–469
azoles for, 354
in bacteria-fungi populations
disseminated infections due to,
318–319
drug resistance and, 317–318
gram-negative bacteria and, 319–320
gram-positive bacteria and, 320–321
in oral environment, 319
in biofilms, 249–250, 299–315, 317–318
versus C. dubliniensis, 33
cell cycle in
checkpoints of, 119–120
perturbation of, 119
stationary phase of, 119
cell wall of, 157–158
glycoproteins of, 200–214

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polysaccharides in, 197–199
synthesis of, 198
chitin synthesis in, 197
chlamydospore form of, 14
codon reassignment in, 46
colonization by, 283–287
CUG codons of, 49–54
dissemination of, 289–294
distribution of, 14, 225–226, 453–458
escape mechanisms of, 160–161
gene families of, 31–33
genetic code of, 49–53
genetic instability in, 57–74
aneuploidies in, 58–60
DNA repair and, 60–65
drug resistance derived from, 65–67
heterozygosity and, 57–58
point mutation and, 57–58
spontaneous versus induced, 67–68
genetic interaction screening in,
497–500
genetics of, 14
genome of, 27–34, 37–38, 505–510
histatin action against, 185–194
horizontal gene transfer to, 37
hyphal form of, 14
immunity modulation and, 268–270
infections due to, see Candida albicans
infections
interspecies interactions with, 321
invasive properties of, 272–274, 287–289
kidney invasion by, 290–291
liver invasion by, 291–294
mating in, 14
bioﬁlm formation and, 309
demonstration of, 76–77
host interactions with, 81
pheromones in, 78–80, 84–85
same-sex, 80
switching role in, 83–84
mating locus of, 75–76
mitochondria of, 331–336
morphogenesis of, 331–336
morphological forms of
cell cycle perturbation and, 119
cyclin regulation in, 109–119
distinguishing features of, 104–109
types of, 101–104
mucosal immunity to, 137–154
mutant libraries for, 394–395
ORFeome project, 505–510
organ infections with, 290–294
pathogenicity of, 14–15
pattern recognition receptors for,
157–160
phagocytosis of, 156, 261–262, 264
polyenes for, 347
protein microarray for, 489–496
proteomic analysis of, 49–51, 262
repetitive DNA elements in, 29–30
resistance in, 65–67, 375–376, 378–379,
388–389, 425
multidrug, 403–411
SC5314
genome of, 28, 30
single nucleotide polymorphisms of,
28
27–28
strain variability in, 91–99
stress responses in, 225–242, 264–267
switching in, 14–15, 82–83
discovery of, 77–78
host interactions with, 81
regulation of, 81–83
role in mating, 83–84
transcriptomic analysis of, 262
tRNA of, 46–47
two-hybrid system for, 483–487
virulence of, 15–16
WO-1
genome of, 28, 30
28
yeast form of, 14
Candida albicans infections
animal models for, 2
candidemia, 431–432
central nervous system, 434
drugs for, 391, 393–394
endophthalmitis, 432–433
gene expression in, 283–298
incidence of, 388
invasive, immunology of, 128–133
oropharyngeal, 419
probiotics for, 321–322
quorum sensing in, 322–324
risk factors for, 2, 389–390
vulvovaginal, 422–424
Candida apicola
antifungal susceptibility of, 465–467
distribution of, 453
Candida bracarensis, 18, 454, 462–463
Candida cifferrii
antifungal susceptibility of, 465,
466–467
Candida colliculosa
antifungal susceptibility of, 466
Candida cylindracea, codon reassignment in,
46
Candida dubliniensis
versus C. albicans, 33
antifungal susceptibility of, 467, 469
azoles for, 354
cell wall of, glycoproteins of, 203–208
in CTG clade, 9
description of, 18
distribution of, 453–454, 461–462
genome of, 27, 29–30, 32–34, 37–38
immunity modulation and, 270
infections due to, 18, 419
mating in, 77–78, 84, 86
mating type-like locus of, 34
mitochondria of, 338
MLST methods for, 94
as new species, 92
phagocytosis of, 264
phylogeny of, 27
in polymicrobial populations, 321
quorum sensing in, 322
repetitive DNA elements in, 29, 30
resistance in, 404–405
single nucleotide polymorphisms of, 27
stress responses in, 227, 235
switching in, 78, 84, 86
vaccines for, 176
Candida famata, 16
antifungal susceptibility of, 350, 466,
469
distribution of, 453–454
Candida fermentati, distribution of,
454, 462
Candida Gene Order Browser, 38
Candida Genome Database, 15, 36–37
Candida glabrata
adhesins of, 250–253, 273
antifungal susceptibility of, 16–17,
349–350, 465–469
in bioﬁlms, 252, 299
Candida albicans interactions with, 321
carbohydrate-active enzymes of, 199
cell wall of, 211
structure of, 250
distribution of, 16, 453–459
echinocandins for, 345, 359
gene families of, 31
genome of, 29, 31, 34, 38
immunity modulation and, 269–270
infections due to, see Candida glabrata
infections
meiosis in, 34–35
mitochondria of, 335–336, 338
MLST methods for, 94–95
nutrient starvation in, 268
phagocytosis of, 264–266
polyenes for, 347
probiotic effects on, 321–322
properties of, 16–17
proteomic analysis of, 262
related to CTG clade, 11
resistance in, 66, 373, 375–376, 379, 389
multidrug, 403–405, 408, 411–412
stress responses in, 227, 229–230,
234–235, 264–266
vaccines for, 175, 176
Candida glabrata infections, 16–17
drugs for, 393
incidence of, 388
invasive, 127
mucosal, 425
oropharyngeal, 419
vulvovaginal, 424
Candida guilliermondii
azoles for, 354
in CTG clade, 11
description of, 18
distribution of, 453–456, 458, 461
genome of, 27, 29–32, 34–35, 37
infections due to, 18, 419
meiosis in, 34–35
phylogeny of, 27
resistance in, 375, 377, 389
Candida haemulonis

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514 INDEX
Candida holmii
Candida humicola
Candida inconspicua, 18
distribution of, 453, 461
Candida intermedia
Candida kefyr, 18
resistance in, 375
Candida krusei
465–469
description of, 18
infections due to, see Candida krusei
infections
polyenes for, 347
related to CTG clade, 11
resistance in, 373, 375–376, 379, 389,
403
vaccines for, 175
Candida krusei infections, 18
invasive, 127, 131–132
mucosal, 425
oropharyngeal, 419
Candida lambica
Candida lipolytica, 18
469
meiosis in, 34–35
Candida lusitaniae, 11
465–469
azoles for, 354
in CTG clade, 10
description of, 18
distribution of, 453–455, 458, 461
genome of, 27, 31–32, 34–35, 37
infections due to, 18
phylogeny of, 27
resistance in, 375, 377, 389
Candida marina
Candida metapsilosis, 17, 92
discovery of, 11
genome of, 29, 34
repetitive DNA elements in, 29
Candida nivariensis, 18, 454, 462
Candida norvegensis, 18
Candida orthopsilosis, 17, 92
discovery of, 11
genome of, 29, 34
Candida parapsilosis
465, 467, 468
azoles for, 354
in bioﬁlms, 299, 304
in CTG clade, 11
description of, 17
distribution of, 17, 453–460
genome of, 27, 29–34, 36–37
groups of, 92
horizontal gene transfer to, 36–37
infections due to, see Candida parapsilosis
infections
mitochondria of, 331–333, 335, 338
phylogeny of, 27
polyenes for, 347
resistance in, 375–376, 378, 389
strains of, 17
vaccines for, 175
virulence of, 17
Candida parapsilosis infections, 17
incidence of, 388
oropharyngeal, 419
Candida pelliculosa
465–469
Candida pulcherrima
Candida rugosa
465–466, 468–469
azoles for, 354
description of, 18
distribution of, 453–454, 461
infections due to, 18
resistance in, 377, 389
Candida sake, 18
Candida sojae
genome of, 29
Candida sphaerica
Candida stellatoidea
Candida subhashii, 91–92
Candida tropicalis, 17–18
adhesins of, 272
465–468
azoles for, 354
in bioﬁlms, 299
Candida subhashii resembling, 91
in CTG clade, 11
distribution of, 453–458, 460
genome of, 27, 29–31, 37
infections due to, see Candida tropicalis
infections
phagocytosis of, 264
phylogeny of, 27
polyenes for, 347
probiotic effects on, 321
resistance in, 375–376, 378, 404–405
switching in, 77–78
vaccines for, 175, 176
Candida tropicalis infections, 17–18
incidence of, 388
oropharyngeal, 419
Candida utilis
Candida valida
Candida zeylanoides, 18
CandidaDB, 37
Candidal infections, see Candidiasis
Candidemia, 429–432
clinical characteristics of, 429–430
costs associated with, 463–465
drugs for, 430–432
epidemiology of, 449–480
shifts in, 451–452
species distribution, 453–463
immunology of, 127–136
incidence of, 388
length of stay in, 463–465
mortality in, 373–376, 463–465
organisms causing, 17–18
protein microarray analysis in, 489–496
proven, 431
reservoirs for, 453
risk factors for, 430, 449
treatment of, 430–432
Candidiasis
deep-organ, see Deep-organ infections
disseminated, see Disseminated
candidiasis
esophageal, see Esophageal candidiasis
gastrointestinal, see Gastrointestinal
candidiasis

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Index 515
history of, 11
incidence of, 387–388
oropharyngeal, see Oropharyngeal
candidiasis
species causing, 11–18; see also specific
species
vulvovaginal, see Vulvovaginal
candidiasis
Candiduria, 435
CaNdt80 protein, in multidrug resistance,
408–409
Cap1 protein
in cell cycle, 107
in stress response, 228, 233–234, 266,
278
Car proteins, in invasion, 288
Carbohydrate-active enzymes, 199
Carbon
acquisition of
in kidney lesions, 290–291
metabolism of, mitochondria in, 336–337
starvation of, 268
CARD9 pathway
in immune response, 159
in invasive candidiasis, 129
Cardiovascular candidiasis, 434–435
CaRep1 protein, in multidrug resistance,
409–410
Cas5 protein, in cell wall, 198
Caspase, in immune response, 160
Caspofungin, 2358–360
advantages of, 346
dosing of, 351
susceptibility to, 465, 468
targeting mitochondria, 335
Cat proteins, in stress response, 265–266
Catalases, in stress response, 227–228,
265–266
Catheters
as candidiasis risk factors, 1
protocol for, 4
Cbk proteins, in biofilm formation, 301,
304, 306
Ccn1 protein, in cell cycle, 110, 111, 116
CD11b/CD18, immunity modulation and,
270
Cdc5 protein, in cell cycle, 119
Cdc19 protein, in kidney lesions, 290
Cdc28 protein, in cell cycle, 111, 117, 119
Cdc42 protein
in bud site selection, 106
in cell cycle, 107–108
Cdc proteins, in cell cycle, 108–109
Cdr proteins
in biofilm formation, 304
in drug resistance, 65–66, 310, 335–336
in general stress response, 230
in multidrug resistance, 404–405,
407–408
Cek proteins
in cell wall, 198, 215
in fungal-bacterial interactions, 321
in histatin response, 190
in mating, 79, 84
in stress response, 230–231
Cell cycle
cell biological features and, 104–109
checkpoints in, 119–120
morphological forms and, 101–104
perturbation of, 119
stationary phase in, 119
Cell dispersal, in biofilm formation,
306–308
Cell elongation, 108
Cell surface protein microarray, for Candida
albicans, 489–496
Cell wall, 197–223
assembly of, gene families for, 32–33
biosynthesis of, 214–216
histatin binding to, 187–188
immune system recognition of, 157–158
pga30 proteins in, 33
polysaccharides of, 197–199
remodeling of, 198, 215–216
structure of, 157, 243
synthesis of, 198
Cell-cell communication, in biofilms,
308–309
Cell-mediated immunity, in invasive can-
didiasis, 130–132
Central nervous system, candidiasis of, 434
Central venous catheters
as candidiasis risk factors, 1
protocol for, 4
Centromeres, 29–30
Cerebrospinal fluid, Candida in, 434
CFEM domains
in proteins, 209–210
Cfl proteins, in liver lesions, 293
CgFlu1 protein, in multidrug resistance, 404
CGOB online tool, 38
CgPDR1 transcription regulator, in drug re-
sistance, 376
Chaperones, heat shock proteins as, 226
Checkpoints
function of, 119–120
genes for, 115
Cheilitis, 420
Chemokines, in oropharyngeal candidiasis,
139
Chemotaxis, defenses against, 270
Chitin, in cell wall, 157, 243
in biofilm formation, 305–306
synthesis of, 197
Chitin synthase inhibitors, 396
Chitinases, in cell wall, 202
Chk1 protein
in cell wall, 198
in quorum sensing, 323
in stress response, 232
Chk proteins, in stress response, 233
Chlamydospores, morphology of, 103–104
7-Chlorotetrazolo[5,1-c]benzo[1,2,4]
triazine, targeting mitochondria,
335
Chromatin deacetylase, in switching, 82
Chronic disseminated candidiasis, 128, 433
Chronic mucocutaneous candidiasis, 137
gene polymorphisms in, 161–162
inflammatory response in, 128
Chs chitin synthases, 197
Cht proteins
in dissemination, 290
Circulatory system, Candida access to, 289
Cit proteins
in mating, 84
Clavispora lusitaniae, 11, 34
Clb proteins, in cell cycle, 111, 117
Cln3 protein, in cell cycle, 110, 111, 119
Clotrimazole, for mucosal candidiasis, 421
Coccidioides immitis
azoles for, 354
polyenes for, 347
Codon(s), see also specific codons
reassignment of, 45–46
Cofitness test, in drug development, 395
Coinhibition profile, in drug development,
395
Colonization
of gastrointestinal tract, 283–285
of oral epithelium, 285–287
of vaginal epithelium, 287
Commensalism, in gastrointestinal tract,
283–285
Commercial testing kit, for strain variation,
91
Comparative expression profiling, in drug
development, 393–394
Comparative genome hybridization, in
strain variation, 94
Complement, in immune response, 156
Complement receptor 3, in immune re-
sponse, 156
Complementation approach, in mating, 76
Complex haploinsufficiency, in genetic
screening, 497–498
Compound libraries, for drug discovery,
392–393
Concentration-dependent killing, 346
Confocal microscopy, 501–503
CPH1 gene, Candida albicans, 14
Cph proteins
in mating, 79, 80, 84, 85
“Crabtree-positive” and “Crabtree-
negative” organisms, 334, 337
Crd1 protein, in general stress response,
230
Crh proteins, in cell wall, 202, 204, 211–213
Crk1 protein, in biofilm formation, 308
Crm1 protein, in multidrug resistance, 410
Cryptococcus
polyenes for, 3
Cryptococcus neoformans
azoles for, 354
invasive properties of, 274
resistance in, 378
Crz1 protein
in cell wall, 198

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516 INDEX
Csa proteins
in cell wall, 202, 205–206, 210
Csh1 protein
in mating, 84
CTA2 gene family, 33
Cta proteins
in heavy metal stress response, 229
in oxidative stress response, 277, 278
Ctf1 protein, in carbon starvation, 268
CTG clade
CUG codon reassignment in, 46–48
genetic code of, 45–55
genomes of, 27–43
members of, 11, 27; see also specific
members
Ctr proteins, in liver lesions, 293
Cts1 protein, in biofilm formation, 306
C-type lectin receptors
in immune response, 156, 159–160
CUG codons
ambiguity of, 49, 51
reassignment of, 46–48
usage of, 51–54
CUN codons, reassignment of, 48
Cyanide and azide (complex IV), in respi-
ration, 331–336
Cyclin(s), 109–119
G1, 110, 117
genes for, 111
hypha-specific, 117–118
mitotic, 111, 116–117
Pcl, 118–119
Cyclin-dependent kinases, in cell cycle,
101
Cyr1 protein, in cell cycle, 107
Cys3 protein, in heavy metal stress re-
sponse, 229
Cystic fibrosis, polymicrobial infections in,
320
Cytokines
in immune response, 156–157
in oropharyngeal candidiasis, 139
in resistance, 128
Cytokinesis, in cell cycle, 108–109
Cytoplasmic cables, in cell cycle, 106–107
Czf1 protein
in biofilm formation, 301, 306, 309
in mating, 80
in switching, 82–83
D
Danish Center for Biological Sequence
Analysis, glycoprotein data in,
201–202, 208
Databases, genome, 36–38
Daughter cells
in mating, 76–77
polarized, 107
DC-SIGN
in immune response, 156, 157, 160
in invasive candidiasis, 129–130
Dcw1 protein, in cell wall, 203
Ddr48 protein, in histatin response, 190
Debaryomyces hanseii, 27
gene families of, 31
genome of, 30–31, 34, 36–37
Debridement, for osteomyelitis, 435
Dectin(s)
gene polymorphisms in, 162
Dectin-1 defects
as candidiasis risk factor, 2
Deep-organ infections, 432–436
cardiovascular system, 434–435
central nervous system, 434
endophthalmitis, 432–433
gastrointestinal, 433–434
hepatosplenic, 433
intra-abdominal, 433–434
kidney, 290–291
liver, 291–294
osteomyelitis, 435
pneumonia, 436
septic arthritis, 435
urinary tract, 435–436
“De-escalation” antifungal therapy, for dis-
seminated candidiasis, 3
Defensins, in oropharyngeal candidiasis,
140
Dendritic cells
Dental caries, microbial populations on,
319
Denture stomatitis, 140, 146, 420
Dgf5 protein, in cell wall, 203
Diagnostic tests, 2–3
Dimorphism, Candida albicans, 14–15
Diploid sequence type, in genetic instabil-
ity, 57–58
Disseminated candidiasis
animal models for, 2, 4, 95–96
antifungal agents for, 3–5
chronic, 128, 433
diagnostic tests for, 2–3
epidemiology of, 171–172
from gastrointestinal candidiasis, 141
from oral candidiasis, 140
organ infections with, 290–294
origin of, 5
polymicrobial, 318–319
risk factors for, 1–2, 171–172
strain variation in, 95
vaccines for, 171–184
DNA, extracellular, in biofilm formation,
308
DNA damage
repair of, 60–65, 111–113
reversal of, 62–65
DNA elements, repetitive, 29–30
DNA repair
genes for, 111–113
Dose fractionation, 346–347
Dot proteins, in oxidative stress response,
278
Double-strand break repair, 63–64
Drug resistance, 373–385; see also individual
drugs, resistance to
acquired, 378
in biofilms, 309–310, 317–318
drug discovery and, 388–389
genetic instability in, 65–67
intrinsic, 376–378
invasive candidiasis mortality and,
373–376
molecular testing for, 379–380
multi-, see Multidrug resistance
pathogen virulence and, 375–376
strain variation in, 96–97
susceptibility testing and, 378–379
temporal trends in, 376–378
treatment failure due to, 378
Dur1 protein, in nutrient starvation, 268
Dur3 protein, in histatin transport, 188
DYRK kinase, in biofilm formation, 306
E
Eap1 protein
adhesive properties of, 248–249
in biofilms, 249–250, 301, 305
in cell wall, 210
in mating, 84
Ece1 protein
in cell cycle, 119
in invasion, 288
in mating, 79
Ece proteins, in mating, 80
Echinocandins, 358–360; see also individual
drugs
new, 396
resistance to, 65–67, 376–378
Ecm proteins, in cell wall, 202, 203
Economic costs, of candidiasis, 390–391
EFG1 gene, Candida albicans, 14
Efg1 protein
in Als regulation, 247
in switching, 82–83
Efg proteins, in cell cycle, 119
Efh proteins, in colonization, 284
Efungimab, 3, 175
Electron transport chain complexes, 331
Empirical therapy, for disseminated candid-
iasis, 3
Ena proteins, in kidney lesions, 291
Endocarditis, 434–435
Endocytosis, 272
Endonucleases, in DNA repair, 63
Endophthalmitis, 432–433
Endothelial cells
adhesion to, 289
Als protein adhesion to, 245–246
Candida interactions with, 262, 289–290
dissemination through, 289–290
Epa adhesion to, 251
Enterobacter cloacae, Candida albicans inter-
actions with, 318
Enterococcus faecalis, Candida albicans inter-
actions with, 318

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Epa proteins
adherence properties of, 270–272
binding specificities of, 251
of Candida glabrata, 16, 250–253
functions of, 250–251
Epithelial cells
Als protein adhesion to, 245–246
Candida interactions with, 262
Epa adhesion to, 251
invasion of, 288–289
oral, colonization of, 285–287
vaginal, colonization of, 287
Erg proteins
in dissemination, 290
in resistance, 65–67, 309, 405, 408
Erythematous oropharyngeal candidiasis,
12
Escherichia coli
Candida albicans interactions with, 320,
321
Candida glabrata interactions with, 321
Esophageal candidiasis
drugs for, 420, 421
risk factors for, 2
Etest, for susceptibility, 466
EU-OPENSCREEN, 392
Euplotes crassus, codon reassignment in, 46
EUROSCARF library, 393
Exg proteins, in cell wall, 201, 203
Exopolysaccharides, in biofilms, 308
Exportin (Crm1 protein), in multidrug re-
sistance, 410
Extracellular DNA, in biofilm formation,
308
Extracellular matrix, in biofilm formation,
306–308
Eye, candidiasis of, 432–433
F
Far proteins, in mating, 79–80
Farnesol
as biofilm inhibitor, 302
in cell cycle inhibition, 119
in quorum sensing, 308–309, 322–324
Fbp1 protein, in carbon metabolism, 336
Fcr proteins
in multidrug resistance, 411
Ferritin, 293
Fet proteins, in liver lesions, 293
Filamentation, 323
in biofilm formation, 304–306
in mating, 80, 85
mitochondria and, 334
Filaments, 33
Fingerprinting, for Candida strain variation,
92, 94
Fitness test, in drug development, 394–395
Fkh2 protein
in cell cycle, 119
Fks proteins
in cell wall, 199
in drug resistance, 376
Flavohemoproteins, in nitrosative stress re-
sponse, 228
Flo proteins
adhesive properties of, 253–254
Flu1 protein, in multidrug resistance, 404
Fluconazole
advantages of, 346
for cardiovascular candidiasis, 434–435
434
for disseminated candidiasis, 3
dosing of, 350
for hepatosplenic candidiasis, 433
for invasive candidiasis, 388–389
for osteomyelitis, 435
for peritonitis, 433–434
pharmacodynamics of, 356
pharmacokinetics of, 355
resistance to, 336–337, 375–378,
388–389, 404–412
susceptibility to, 465–468
for vulvovaginal candidiasis, 424
Fluconazole-amphotericin B deoxycholate,
for disseminated candidiasis, 3
Flucytosine
advantages of, 346
434
clinical uses of, 352
dosing of, 350
pharmacodynamics of, 352
resistance to, 403
toxicity of, 352
Fluorescent markers, for Candida imaging,
501–503
5-Fluorocytosine, see Flucytosine
Fox proteins
in carbon starvation, 268
in invasion, 288
Fps1 protein, in osmotic stress response,
227
Frataxin, in respiration, 334
Fre proteins
Frg23 protein, in mating, 80
Ftr proteins, in liver lesions, 293
Fungal Genome Initiative, 37
Fungi Imperfecti, 11
Funspec algorithm, 393
Fusarium
azoles for, 354
polyenes for, 347
Fusobacterium nucleatum, in polymicrobial
populations, 321
G
Gain-loss theory, of codon reassignment, 46
Gal proteins
in carbon metabolism, 335–336
in methyl mismatch repair, 60–61
Galectin(s)
Galectin-3 receptor, in immune response,
157
Gas proteins, in cell wall, 202, 206, 211,
215
Gastrointestinal candidiasis, 433–434
dissemination of, 141
immunity to, 140–142
Gastrointestinal tract
Candida in, 12
commensalism in, 283–285
surgery on, as candidiasis risk factor, 1–2
Gca proteins, in biofilm formation, 301,
307–308
Gcn4 protein, in biofilm formation, 307
Gene families, 30–33
Gene Ontology, in drug development, 393
Gene transfer, horizontal, 35–37
General stress response, 229–230
Genetic code, of CTG clade, 45–55
Genetic instability, 57–74
aneuploidies in, 58–60
DNA repair and, 60–65
drug resistance derived from, 65–67
heterozygosity and, 57–58
point mutation and, 57–58
spontaneous versus induced, 67–68
Genetic interaction screening, for Candida
albicans, 497–500
Genetics, Candida albicans, 14
Génolevures database, 38
Genome(s), 27–43; see also individual organ-
isms, genome of
databases for, 36–38
gene families, 30–33
horizontal gene transfer, 35–37
mating type-like locus, 34
meiosis, 34–35
rearrangement of, strain variation and,
94
single nucleotide polymorphisms in,
27–28
Geographical locations, strain variation
and, 95
Germ tubes, formation of, 106, 110
Gin proteins, in biofilm formation, 301,
306
β-Glucan(s), in cell wall, 157–158
β-1,2-Glucan, in cell wall, 157–158,
443–445
β-1,3-Glucan, in cell wall, 197, 199
β-1,6-Glucan, in cell wall, 199
Glucan antibodies, for vaccines, 174–175
Glucanosyltransferases, in cell wall, 202,
211
Gluconeogenesis, carbon starvation and,
268
Glutathione, in stress response, 266
Glutathione peroxidase, in stress response,
227
Glyceroaquaporin, in osmotic stress re-
sponse, 227
Glycerol, accumulation of, in osmotic stress
response, 227

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Glycerol-3-phosphatase, in osmotic stress
response, 227
Glycerol-3-phosphate dehydrogenase, in
osmotic stress response, 227
Glycolases, in DNA repair, 62
Glycolysis
mitochondria in, 336–337
Glycoproteins, cell wall, 200–214
anchoring processes of, 200
functions of, 214
glucanosyltransferases in, 211
GPI-anchored, 200–201, 203–208
Pir group, 201
Plb family in, 213
Sap family in, 213
Sod family in, 213
soluble, 200
structural variations in, 201–202, 208
study methods for, 213–214
subgroups of, 200
surface, 210–211
tandem repeats in, 208–210
transglycosidases in, 211–213
Glycoside hydrolases, in cell wall, 202
Glycosylphosphatidylinositol-anchored
proteins, 200, 202–208, 243–254
Glyoxalate cycle, carbon starvation and, 268
Gnc proteins, in biofilm formation, 301
Gnp proteins, in invasion, 288
Goa proteins
in respiration, 338–339
Gpd proteins, in stress response
general, 230
osmotic, 227
Gpm proteins
in oxidative stress response, 278
Gpp1 protein, in osmotic stress response,
227
Gpx1 protein, in oxidative stress response,
277
GRACE approach, to drug discovery, 394
Green fluorescent protein yeast, in Candida
imaging, 501–503
Gross chromosomal rearrangements, in ge-
netic instability, 59, 66–67
Grp proteins
Gsh proteins
Gst3 protein, in oxidative stress response,
278
Gys1 protein, in oxidative stress response,
278
H
Haemophilus influenzae, vaccines for, 173
Hal proteins, in invasion, 288
Haploinsufficiency, in genetic screening,
497–498
Hcg1 protein, in dissemination, 289–290
Hda1 protein, in switching, 82
Heart, candidiasis of, 434–435
Heat shock, response to, 226–227
Heat shock protein antibodies, for vac-
cines, 175
Heavy metal stress response, 229
Helicases, in immune response, 158
Hepatosplenic candidiasis, 433
Heterozygosity, genetic instability and,
57–58
Hgc1 protein, in cell cycle, 101, 110, 111,
117–119
HIS genes, for histatin, 185–194
Histatins, 185–194
binding to Candida, 187–188
Candida response to, 190
cell-specific expression of, 185
family members of, 185–186
fungicidal activity of, 188–190
interaction with membranes, 187
intracellular effects of, 190
levels in saliva, 186
overview of, 185
resistance to, 190
secretion of, 185
targeting mitochondria, 335
uptake of, 188
Histoplasma capsulatum
azoles for, 354
polyenes for, 347
Hit compounds, in drug development, 393
HIV/AIDS
candidiasis incidence in, 387–388
colonization in, 286
histatin levels in, 186
mucosal candidiasis in, 137
oropharyngeal candidiasis in, 12, 172,
419–420
vaccinations in, 172–173
vulvovaginal candidiasis in, 424
Hkr1 protein
in cell wall, 199
Hmx proteins, in liver lesions, 293
Hnt1 protein, in oxidative stress response,
278
Hog1 protein
in respiration, 338
in stress response, 230–233, 266
Homologous recombination
in DNA repair, 63–64
in genetic instability, 57–58
Horizontal gene transfer, 35–37
Hormone replacement therapy, vulvovagi-
nal candidiasis in, 422
Host, environment of
mating process in, 81
switching process in, 81
Hsf proteins
in heat shock response, 226–227
Hsp proteins
in weak acid stress response, 228
Hst7 protein, in mating, 85
Human immunodeficiency virus infection,
see HIV/AIDS
Humoral immunity, 156, 489–496
HWP1 gene, Candida albicans, 15
Hwp1 protein
in biofilm formation, 303, 304, 306, 309
in invasion, 288
Hwp proteins
adherence properties of, 247–248, 272
in biofilms, 249, 301, 306
in cell cycle, 119
in mating, 80
regulation of, 248
Hxt proteins, in kidney lesions, 290
Hydrolases, in immunity modulation, 269
Hydroxyl radical, stress response to,
227–228
Hyper-immunoglobulin E syndrome
autosomal dominant, 132
gene polymorphisms in, 161
Hypermutable cell populations, 67–68
Hyperosmotic stress response, 227
Hyperpolarization, bud formation in, 278
Hyphae, morphology of, 101–103,
299–300
Hyr proteins
adherence properties of, 272
in cell wall, 207
Hyr/Iff protein family, 32–33
I
Icl1 protein
in invasion, 288
Icofungipen, 396
Ifa proteins, 33
Ifd proteins, in biofilm formation, 301, 307,
308
Iff proteins
adherence properties of, 272
in cell wall, 201, 207, 210–211
Ifh proteins, in heavy metal stress response,
229
Imidazoles, 354
Immune reconstitution inflammatory syn-
drome, 128
Immunity
adaptive, see Adaptive immunity
Candida survival strategies in, 261–282
innate, see Innate immunity
modulation of, 268–270
mucosal, see Mucosal immunity
Immunization, see Active immunization;
Passive immunization; Vaccines
Immunodeficiency, see also HIV/AIDS
invasive candidiasis in, 172–174
oropharyngeal candidiasis in, 12
vulvovaginal candidiasis in, 423
Immunology, of invasive candidiasis,
127–136
Immunoregulation, in gastrointestinal
tract, 142
Indolamine 2,3-dioxygenase, in resistance,
128, 132–133
Infections, candidal, see Candidiasis
Infectious Diseases Society of America, sus-
ceptibility testing guidelines of, 379
Inflammasomes, in immune response, 160
Inflammatory response
in candidiasis, 128
innate immunity in, 156

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Innate immunity, 155–170
adaptive responses in, 157
adjuvant therapy and, 163–164
Candida cell wall and, 157–158
Candida escape from, 160–161
Candida killing capacity and, 156–157
genes of, polymorphisms of, 161–163
host susceptibility and, 161–163
killing of organisms in, 156
pattern recognition receptors in,
157–160
phagocytosis in, 156
Instability, genetic, see Genetic instability
Integrins, immunity modulation and, 270
Interaction assay, for Candida albicans,
483–487
Interferon-γ
Interleukin(s)
in oropharyngeal candidiasis, 139–140
in resistance, 128
Interleukin-10, in invasive candidiasis, 132
Interleukin-17, in innate immunity, 157
Intra-abdominal candidiasis, 433–434
Intracellular trafficking, interference with,
269–270
Invasive candidiasis, see also Candidemia;
Disseminated candidiasis
biomarkers for, 443–446
costs associated with, 463–465
definition of, 12
diagnosis of, 388, 445–446
drugs for, 388–391, 445–446, 465–469
epidemiology of, 443, 449–480
community onset, 451–452
incidence, 449–451
species distribution, 453–463
host niche status and, 226
acquired immunity in, 130–132
dendritic cells in, 130
innate immune receptors in, 129–130
resistance, 127–128, 132–133
shaping of, 128–132
tolerance, 127–128, 132–133
incidence of, 12–13, 127, 388
length of stay in, 464–465
mechanisms of, 272–274
mortality in, 373–376, 463–465
organisms causing, 12–14
reservoirs for, 453
risk factors for, 463
Ipf proteins, in oxidative stress response,
278
Ire1 protein, in biofilm formation, 301, 306
Iron, stress response to, 229
Iron acquisition
Als proteins and, 246
Isavuconazole, 396
Isw2 protein, in oxidative stress response,
278
Itraconazole
advantages of, 346
for candidemia, 431
dosing of, 350
drug-drug interactions of, 353, 357
monitoring of, 356
toxicity of, 357
for vulvovaginal candidiasis, 424
J
Joint infections, 435
K
Kar2 protein, in histatin response, 190
Kem1 protein, in biofilm formation, 301,
304
Ketoconazole, for vulvovaginal candidiasis,
424
Kgd proteins, in liver lesions, 292
Kidney, Candida invasion of, 290–291,
435
Killing, of Candida, 156
Klebsiella pneumoniae, Candida albicans in-
teractions with, 318
Knr4 protein, in cell wall, 199
Kre6 protein, in histatin response, 190
Kre proteins, in cell wall, 207
Kynurenines, in resistance, 128, 132–133
L
Lactic acid, stress response to, 228–229
Lactobacillus
gastrointestinal, 142
vaginal, 422–423
Lactobacillus acidophilus, for candidiasis, 322
Lactococcus lactis, for candidiasis, 321–322
Lamp proteins, in intracellular trafficking,
270
Lanosterol demethylase, in drug resistance,
65
Leishmania, histatin action against, 185
Libraries, for drug discovery, 392–395
Lif1 protein, in DNA repair, 64
Lig proteins, in DNA repair, 64
Lip proteins
in invasion, 288
Lipases, in immunity modulation, 269
Liposomal amphotericin, 175
Liver, Candida invasion of, 291–294, 433
Lodderomyces elongisporus, 27
cell wall of, 210–211
gene families of, 31, 33
glycoproteins of, 210
phylogeny of, 27, 29, 33–34, 36–37
27–28
Long terminal repeats, 30
Loss of heterogeneity, 28, 94–95
Loss of heterozygosity, genetic instability
and, 57–58
Lsp1 protein, in mating, 84
Lung, Candida invasion of, 436
M
Macrophages, in immune response, 156,
157
Mad2 protein, in cell cycle, 119–120
MAG1gene, in DNA repair, 62
Magnaporthe grisea, cell wall of, 210
Major facilitator superfamily transporters,
Major repeat sequences, 29, 94
Mak proteins, in stress response, 232–233
Mal proteins, in liver lesions, 292
Mannan
antibodies to
as biomarker, 445
for vaccines, 174
in cell wall, 157
Mannoproteins, in cell wall, 157, 243
Mannose receptor
in immune response, 156, 159
Mannose-binding lectin, in immune re-
sponse, 156
MAPK (mitogen-activated protein kinase)
pathway, in stress response,
230–232
Mating
Candida albicans, see Candida albicans,
mating in
demonstration of, 76–77
host environment for, 81
pheromones in, 78–80, 84–85
same-sex, 80
switching requirements for, see
Switching
Mating locus, Candida albicans, 75–76
Mating type-like locus, evolution of, 34
Mcm1 protein, in multidrug resistance, 409
MDR1 gene, in multidrug resistance,
404–407, 409–410
Mdr1 protein
in drug resistance, 66, 310
Mds proteins, in biofilm formation, 302,
304
Mechanical ventilation, 319–320, 436
Meiosis, evolution of, 34–35
Meningitis, 434
Met proteins
in invasion, 288
Methyl mismatch repair, 60–61
N-Methyl-N′-nitro-N-nitrosoguanidine, in
DNA repair, 62
MFα1 gene, in mating, 78–80
MFA1 gene, in mating, 79
MFM complex, in mitochondrial function,
337–339
MGCD290 (histone deacetylase inhibitor),
396
MGT1 gene, in DNA repair, 62
MIC (minimum inhibitory concentration),
346–347
Micafungin, 2358–360
advantages of, 346

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Micafungin (continued)
dosing of, 351
Miconazole, for mucosal candidiasis, 421,
425
Microarray analysis, for Candida albicans,
489–496
Microbial populations and communities,
317–330
on abiotic surfaces, 317–318
in biofilms, 317–318; see also Biofilms
in disseminated infections, 318–319
gram-negative bacteria in, 319–320
gram-positive bacteria in, 320–321
non-Candida species in, 321
in oral environment, 319
probiotics and, 321–322
quorum sensing in, 322–324
resistance in, 317–318
Microscopic examination
of animal, 501–503
for vulvovaginal candidiasis, 423–424
Microtubules, 106
Mid1 protein, in cell wall, 201
Miltefosin, 396
Mincle
Minimum inhibitory concentration (MIC),
346–347
Mitochondria, 331–341
in Candida, 331–337
carbon metabolism and, 336–337
description of, 331
as drug targets, 335–336
environmental niches and, 336–337
functions of, 331–339
histatin interactions with, 188–189
historical perspective of, 331
in Saccharomyces cerevisiae, 337–339
structure of, 337
Mitogen-activated protein kinase pathway,
Mitotic cyclins, 116–117
Mitotic recombination, in strain variation,
94
Mkc1 protein
in cell wall, 198
in drug resistance, 310
in stress response, 230, 232
Mlc1 protein, in cell cycle, 107
Mls1 protein
in invasion, 288
Mnl1 protein, in stress response, 229, 234
Mode of action, in drug development,
393–395
Molecular Libraries Program Centers Net-
work, 392
Molecular testing, for drug resistance,
379–380
Monocytes, in immune response, 156
Morphogenesis
biofilm formation and, 299–300
of Candida albicans, 331–336
in oxidative stress, 278
in phagocytosis, 262, 264
Morphogenesis checkpoint, 119–120
Morphological forms, Candida
cell cycle checkpoints in, 119–120
cell cycle perturbation and, 119
distinguishing features of, 104–109
in stationary phase, 119
types of, 101–104
Morphology index, 104
Mortality, drug resistance related to,
373–376
MRX complex, in DNA repair, 64
Msb2 protein
Msn proteins, in stress response, 229, 234
MTL genes, in mating, 75–76, 78, 81
MTT assay, in drug development, 393
Mucocutaneous candidiasis, chronic, see
Chronic mucocutaneous
candidiasis
Mucosal candidiasis, see also Esophageal
candidiasis; Gastrointestinal can-
didiasis; Oropharyngeal candidiasis;
Vulvovaginal candidiasis
anatomical sites of, 419
diagnosis of, 424–425
overview of, 419
pathogenesis of, 425
treatment of, 421
vaccine for, 425
Mucosal immunity, 137–154
in biofilms, 145–146
in gastrointestinal candidiasis, 140–142
historical perspective of, 137–138
in oral candidiasis, 138–140
in vaginal candidiasis, 142–145
Multidrug resistance, 403–416
drug target alterations in, 405
drug transport alterations in, 404–405
transcriptional regulation in, 405–412
Multilocus sequence typing, for Candida
strain variation, 92–95
Muramyl dipeptides, in fungal-bacterial in-
teractions, 321
Murine models, for disseminated candidia-
sis, 2
Mut proteins, in methyl mismatch repair,
60–61
Mutant libraries, for drug discovery,
394–395
Mutation, in strain variation, 94
Mycobacterium tuberculosis, intracellular
trafficking in, 270
Mycograb, 175
Myeloid differentiation factor, in invasive
candidiasis, 129
Myocarditis, 434–435
N
NALP3 protein, in invasive candidiasis,
130
National Nosocomial Infection System sur-
vey, 451
Natural libraries, for drug development,
392–393
Ndt80 protein, in multidrug resistance,
408–409
Neurospora crassa, stress response in, 232
Neutropenia
as risk factor, 1
vaccinations in, 173
Neutrophils
NGT genes, in DNA repair, 62
Niches
Candida albicans, 14, 225–226, 336–337
Candida glabrata, 16
Candida parapsilosis, 17
Nik1 protein, in stress response, 232
Nikkomycin Z, 396
Nitric oxide, stress response to, 228
Nitrogen acquisition
Nitrosative stress response, 228, 264–267,
269
NLRP3 gene, polymorphisms of, 163
Nonhomologous end joining, in DNA re-
pair, 64
Nrg1 protein
in morphology, 103
N-terminal domain, of adhesins, 244
Nth1 protein, in oxidative stress response,
278
Nuclear division, in cell cycle, 108–109
Nuclear migration, 106
Nucleotide binding domain leucine-reach
repeat-containing receptors
Nucleotide excision repair, 63
Nup proteins, in biofilm formation, 302,
304
Nutrient acquisition, in kidney lesions,
290–291
Nutrient starvation, 267–268
Nystatin
liposomal formulation of, 396
O
Och1 protein, in biofilm formation, 302
Odynophagia, in oral candidiasis, 420
OGG1 gene, in DNA repair, 62
Op4 protein
in mating, 80
in switching, 81
Opaque cells, see also Switching
in mating, 76–78, 81
morphology of, 103–104
Opb proteins, in mating, 76
Opportunistic infections, 12
versus accidental infections, 1–2
Opre protein, in mating, 84
Oral contraceptives, vulvovaginal candidi-
asis due to, 422
Oral environment, microbial populations
in, 319
Orf19.207 protein, in mating, 84
ORFeome project, Candida albicans,
505–510
Oropharyngeal candidiasis
areas affected in, 138
biofilms in, 146
clinical manifestations of, 420
denture stomatitis, 140, 146

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diagnosis of, 420
drugs for, 420, 421
epidemiology of, 419
in immunodeficiency, 137
incidence of, 387–388
intraspecies interactions in, 321
pathogenesis of, 420
risk factors for, 2, 172
species causing, 11–12
treatment of, 420, 421
vaccines for, 172
Osmotic stress response, 190, 227
Osteomyelitis, 435
Oxidation, in Candida killing, 156
Oxidative stress response, 227–228,
264–267
farnesol in, 323
mitochondria and, 334–335
suppression of, 269
P
Pacemakers, infection of, 435
Pap proteins
in mating, 76
Paracoccidioides
azoles for, 354
polyenes for, 347
Paracoccidioides brasiliensis, farnesol effects
on, 324
Parallel respiratory pathway, 332–333
Passive immunization, 4–5
mechanism of action of, 130–131
Pasteur Institute, database of, 37
Pathogen-associated molecular patterns, in
invasive candidiasis, 129
Pathogenicity, see specific organisms
Pattern recognition receptors, 157–160
Pbr1 protein, in mating, 84
Pbs proteins, in stress response, 230–231
Pck1 protein
Pcl proteins, in cell cycle, 111, 117–118
PCR (polymerase chain reaction)
for diagnostic use, 445
for drug resistance, 379–380
Pda proteins, in liver lesions, 292
Pdh1 protein, in multidrug resistance, 405,
408
Pdr proteins
Pdx proteins
Pep1 protein, in switching, 81
Pep12 protein, in biofilm formation, 302
Pepstatin A, in invasion, 272
Peptidoglycans, in fungal-bacterial interac-
tions, 321
Pericarditis, 434–435
Peritonitis, 433–434
Peroxide, stress response to, 227–228
Persister cells, in drug resistance, 310
Pfk proteins
Pga proteins, 33
in cell wall, 201, 203–207, 210
in mating, 84
Pgk proteins, in morphogenesis, 334
Phagocytosis
of Candida, 156, 261–262, 264
defenses against, 270
Pharmacodynamics, of antifungal drugs,
346–347
Pharmacokinetics, of antifungal drugs,
346–347
Pharmacology, of antifungal drugs, 345
Pharyngeal candidiasis, see Oropharyngeal
candidiasis
Phenazines, in polymicrobial populations,
320
Phenotype(s), strain variation due to,
96–97
Phenotype switching, Candida albicans,
14–15
Pheromones
in mating, 78–80, 84–85
Pho84, in kidney lesions, 291
Pho proteins
in cell cycle, 111, 117–118
in invasion, 288
Phosphate acquisition, in kidney lesions,
291
Phospholipases
Candida albicans, 14
Phosphomannan, in cell wall, 157
Phosphorelay systems, in stress response,
232–233
Photolyases, 62
Phr proteins
in cell wall, 202, 206, 211
in invasion, 288
Pichia guilliermondii
Pichia stipitis, 27
Pir proteins
Plagiochin E, targeting mitochondria, 335
Platelia Candida tests, 445
Plb proteins
in invasion, 288
Plc proteins, in immunity modulation, 269
PLD-118 (icofungipen), 396
Pld proteins, in immunity modulation, 269
Pma proteins, in liver lesions, 292
PMS1 protein, in methyl mismatch repair,
60–61
Pmt1 protein, in dissemination, 290
Pmt proteins, in biofilm formation, 302
PNA-FISH analysis, for drug resistance,
379–380
Pneumocystis, farnesol effects on, 324
Pneumonia, 436
Point centromeres, 29–30
Point mutation, genetic instability and,
57–58
Pol proteins, in DNA repair, 64–65
Polarisomes, 107–108
Polyenes, 347–353
new, 396
pharmacokinetics of, 347, 350
resistance to, 403
spectrum of activity of, 347, 349–350
toxicity of, 348
Polymerase chain reaction, see PCR
Polymerases, in DNA repair, 64–65
Polymicrobial populations, see Microbial
populations and communities
Polysaccharides, of cell wall, 197–199
Polystictus versicolor, Spitzenkörper in, 107
Porphyromonas gingivalis, Candida albicans
Posaconazole
advantages of, 346
for candidemia, 431
dosing of, 351
monitoring of, 356
Postantifungal effect, 346
Potassium hydroxide test, for vulvovaginal
candidiasis, 423–424
PqsR protein, in polymicrobial populations,
323
Pra proteins
in intracellular trafficking, 270
in invasion, 288
Pregnancy, vulvovaginal candidiasis in,
172, 422
Preimmunity, to Candida, 173–174
Preseptum, 108
Prey proteins, in two-hybrid system,
483–487
Prh proteins, in mating, 84
Probiotics, for candidiasis, 321–322
Prophylactic antifungal therapy, for dissem-
inated candidiasis, 4–5
Prospective Antifungal Therapy (PATH)
registry, 375
Prosthetic joint infections, 435
Protein microarray, for Candida albicans,
489–496
Proteinases, Candida albicans, 14
Protein-protein interactions, in two-hybrid
system, 483–487
Pruritus, in vulvovaginal candidiasis, 423
Pseudohyphae, morphology of, 101–103,
299–300
Pseudomembranous oropharyngeal candidi-
asis, 16

IP: 201.230.209.68
On: Sun, 11 Aug 2019 00:30:48
522 INDEX
Pseudomonas aeruginosa, Candida albicans
interactions with, 318–320, 324
Pwp proteins, adhesive properties of, 253
Pxa proteins, in invasion, 288
Pyelonephritis, 435
Pyk proteins
Pyrimidine dimers, reversal of, 62
Q
Quorum sensing
in biofilms, 308–309
R
Rad proteins
in cell cycle, 120
in DNA repair, 63–65
Ram1 protein, in mating, 79
Rap1 protein, adherence properties of, 272
Ras1 protein
in cell cycle, 119
in quorum sensing, 322–323
Ras-cAMP signaling
in fungal-bacterial interactions, 320–323
in heat shock, 226–227
in weak acid stress response, 229
Rbt proteins
in cell cycle, 119
in cell wall, 205–206, 210
in colonization, 284–286
in invasion, 288
in mating, 80, 84
Reactive nitrogen species
stress response to, 228, 264–267
suppression of, 269
Reactive oxygen species
in histatin action, 188–189
mitochondria and, 334–335
stress response to, 227–228, 264–267
suppression of, 269
Recombination, in adhesin evolution,
254–255
Reconstituted human epithelial model,
286, 288
Redox-sensitive antioxidants, in stress re-
sponse, 233
Reflectance confocal microscopy, 501–503
Rep1 protein, in multidrug resistance,
409–410
Repair systems, see also DNA repair
DNA
genes for, 111–113
for oxidative stress, 227
Repetitive sequences, 29–30
Reservoirs, for invasive candidiasis and
candidemia, 453
Resistance
to antifungal agents, see Drug resistance;
Susceptibility
to Candida, immunology of, 127–128,
132–133
to histatin, 190
Respiration, in Candida, 331–335
Respiratory burst, in Candida killing, 156,
264–267
Restriction fragment length polymorphism
analysis, in strain variation, 94
Retrotransposons, 30
Rev proteins, in DNA repair, 64–65
Rga proteins
in cell cycle, 117
Rho1 protein, in cell wall, 199
Rif1 protein, adherence properties of, 272
RigI protein, in immune response, 158, 160
Rim proteins
in invasion, 288
in mating, 80
Risk factors, for candidiasis, 1–2
disseminated, 1–2, 171–172
esophageal, 2
oropharyngeal, 2
vulvovaginal, 145, 172
RNA, transfer, 46–47
Rotenone (complex I), in respiration,
331–336
Rpd3 protein, in switching, 82
S
Saccharomyces cerevisiae
Als protein studies in, 246
in biofilms, 305
bud site selection in, 106
cell cycle of, 111–115, 119–120
cell wall of, 157
glycoproteins of, 200, 209, 212,
214–215
polysaccharides in, 197–199
synthesis of, 198
chitin synthesis in, 197
CUN codons of, 46
cyclins of, 110, 117
DNA repair in, 57–60, 62–63, 65
histatin and, 185, 187–188
infections due to, 131–132
mating of, 75, 77, 79–80, 82
mutant library of, 394–395
pseudohyphae of, 101–102
resistance in, 403–404, 408, 411
role in drug discovery, 391, 393–395
septation in, 108
stress response of, 51, 225–235
tRNA of, 47
yapsins in, 213
yeast cells of, 101–102
Salicyl hydroxamic acid pathway, in respi-
ration, 331–336
Salivary histatins, see Histatins
Salmonella enterica serovar Typhimurium,
Candida albicans interactions with,
320
Salt stress, response to, 227
Same-sex mating, Candida albicans, 80
Sap proteins
in cell wall, 202–204, 213
in invasion, 288
in mating, 80
in switching, 81
SAPK (stress-activated protein kinase)
pathway, in stress response, 230–232
SAPs (secreted aspartyl proteinases),
Sas10 protein, in oxidative stress response,
278
Scaffolds, for drug discovery, 392
Scedosporium
azoles for, 354
polyenes for, 347
Schizosaccharomyces pombe
cyclins of, 110
stress responses in, 225–227, 229–230,
232–233
Schmoos, in reproduction, 75
Screening
in drug development, 392
genetic interaction, 497–500
Sdh12 protein, in kidney lesions, 290
Sec proteins, in colonization, 286
Secreted aspartyl proteinases, 30–32
in cell wall, 213
Sed proteins, in cell cycle, 210
Septation, in cell cycle, 108–109
Septic arthritis, 435
Septins
genes for, 114
Ser residues, in adhesins, 244
Serratia marcescens, Candida albicans inter-
actions with, 318, 320
Serum beta glucan test, 3
Sexual transmission, of candidiasis, 423
She3 protein, in cell cycle, 117
Sho1 protein
in cell wall, 198
Single nucleotide polymorphisms, 27–28
Single-strand annealing, in DNA repair,
64–65
Sir proteins, adherence properties of, 272
Skn7 protein, in stress response, 234
Sko1 protein, in cell wall, 198
Sl1 protein, in cell wall, 198
Sln proteins, in stress response, 232
Slt2 protein, in cell wall, 199
Smil protein, in cell wall, 199
Snq2 protein, in multidrug resistance, 405,
408
Sod proteins
in invasion, 288
in liver lesions, 293–294
in oxidative stress response, 264–265,
277
Sorbitol, stress response to, 227
Sordarins, 396
Spa2 protein, in cell cycle, 107–108
Specific codon usage, in Candida albicans,
51–53
Spectrophotometry, in drug development,
393
Spi proteins, in cell cycle, 210
Spinal cord, candidiasis of, 434
Spindles, 106
Spitzenkörper, 107–108

IP: 201.230.209.68
On: Sun, 11 Aug 2019 00:30:48
Index 523
SPK-843 (polyene), 396
Spleen, Candida invasion of, 433
Sporothrix schenckii
azoles for, 354
polyenes for, 347
Spr1 protein, in cell wall, 201
Spt-Ada-Gcn5-acetyltransferase coactiva-
tor complex, in multidrug resis-
tance, 410
Ssa proteins, histatin binding to, 188
Ssk proteins
in oxidative stress, 278
Ssp proteins, in fungal-bacterial interac-
tions, 320
Sst proteins, in mating, 84
Ssu proteins
in invasion, 288
Staphylococcus aureus
in biofilms, 309
317–318, 324
Staphylococcus epidermidis
in biofilms, 299, 309–310
317–318
Starvation, nutrient, 267–268
Stationary phase, of cell cycle, 119
Ste proteins
in mating, 79–80, 84, 85
Stomatitis
denture, 140, 146
in oral candidiasis, 420
STOP codons, 45
Strain variability, 91–99
clinical significance of, 95–97
detection of, 92, 94–95
species assignment and, 91–93
types of, 92, 94–95
Streptococcus anginosus, Candida albicans in-
Streptococcus gordonii, Candida albicans in-
teractions with, 319–321
Streptococcus oralis, Candida albicans inter-
actions with, 319
Streptococcus pneumoniae, vaccines for,
173–174
Streptococcus sanguinis, Candida albicans in-
Streptococcus thermophilus, for candidiasis,
321–322
Stress, genetic instability in, 67–68
Stress responses, 225–242
cellular, 226–230
general, 229–230
heat shock, 226–227
heavy metal, 229
host niches and, 225–226
in liver lesions, 293–294
mitochondria in, 334–335
nitrosative, 228, 264–267
nutrient starvation, 267–268
osmotic, 227
oxidative, 227–228, 264–267, 323,
334–335
in phagocytosis, 264–267
signaling pathways in, 230–233
transcription factors in, 233–235
versus types of stress, 226
weak acid, 228–229
Stress-activated protein kinase pathway, in
stress response, 230–232
Structure-activity relationship, in drug de-
velopment, 393
Sty1 protein, in stress response, 230, 233
Succinate (complex II), in respiration,
332
Sul1 protein, in heavy metal stress re-
sponse, 229
Sun proteins
in mating, 84
Superoxide anions, stress response to,
227–228
Superoxide dismutases, see also Sod
proteins
in oxidative stress response, 264–265
Surgery, as candidiasis risk factor, 1–2
Susceptibility
to drugs, 465–469; see also specific organ-
isms, antifungal susceptibility of
testing for, 378–379
of host, 161–163
Suv proteins, in biofilm formation, 302,
304
Swe1 protein, in cell cycle, 119–120
Switching
in biofilm formation, 305–306, 309
Candida albicans, see Candida albicans,
switching in
Candida dubliniensis, 77–78, 84, 86
cell morphology and, 104
historical view of, 80–81
host environment for, 81
opaque cells in, 81
role in mating, 83–84
Synthetic libraries, for drug development,
392–393
Systemic candidiasis, see Candidemia; Dis-
seminated candidiasis; Invasive
candidiasis
T
T-2307 (acrylamide), 396
T lymphocytes
in gastrointestinal candidiasis, 141–142
Tac1 protein
in drug resistance, 66, 407–408
T-cell receptors, in oropharyngeal candidia-
sis, 139
Tec1 protein
in mating, 84, 85
Teeth, microbial populations on, 319
Telomeres, 29
Tetraploidy, in Candida albicans, 77
Th17 cells
in innate immunity, 157
Thioredoxin
Thr residues, in adhesins, 244
Thrombophlebitis, 435
Th1/Th2 cells
TIM complex, in mitochondrial function,
337–339
TLO proteins, 33
TMP-1363, targeting mitochondria,
336
Tolerance, to Candida, 127–128, 132–133,
142
Toll-like receptors
polymorphisms of, 161
TOM complex, in mitochondrial function,
337–339
Torulopsis, 11
Torulopsis glabrata, see Candida glabrata
Tos9 protein, in switching, 82
Toxicity studies, in drug development,
393
Tps proteins
Tpx1 protein, in stress response, 233
TR region, in Als family, 244–245
Transcription factor complementation, in
two-hybrid system, 483–487
Transferrin, 293
Transglycosidases, in cell wall, 211–213
Translation, molecules of, 45
Translesion synthesis, in DNA repair,
64–65
Translocases, in mitochondrial function,
337–339
Transposable elements, 30
Treg cells
Trehalose, in stress response, 266
heat, 226
oxidative s, 277
Triazoles, 354
TRIF (Toll-IL-1 receptor domain-
containing adapter-inducing beta
interferon) pathway, in invasive
candidiasis, 129
Trp1 protein, in colonization, 286
Trr1 protein, in oxidative stress response,
277–278
Trx1 protein
in oxidative stress response, 277–278
Tryptophan starvation, 132–133
Tsa1 protein, in oxidative stress, 278
Ttr1 protein, in kidney lesions, 291
Tup1 protein
in Als regulation, 247
in cell cycle, 117, 118
Tye7 protein, in carbon metabolism,
335–336
Tyrosol, in quorum sensing, 308

IP: 201.230.209.68
On: Sun, 11 Aug 2019 00:30:48
524 INDEX
U
Uec1 protein, in invasion, 273, 288
Ultraviolet light damage, DNA repair in,
62, 63
Ume6 protein
in cell cycle, 118
in morphology, 102–103
Upc proteins, in drug resistance, 66
URA3 gene, Candida albicans, 15
Ura proteins, in nutrient starvation,
267–268
Urinary tract, candidiasis of, 435
Utr proteins, in cell wall, 202, 204
Uvr proteins, in DNA repair, 63
V
Vaccines, 171–184
for active immunization, 175–178
adjuvants for, 177
barriers to efficacy of, 172–174
development of, 163–164
for passive immunization, 174–175
rationale for, 171–174
Vacuolar inheritance, 108
Vaginal candidiasis, see Vulvovaginal
candidiasis
Vaginal-relapse theory, 423
Ventilator-related infections, 319–320, 436
Virulence factors, see also specific organisms
drug resistance and, 375–376
versus host defenses, 155
strain variation and, 96
stress responses and, see Stress responses
Voriconazole
advantages of, 346
dosing of, 351
monitoring of, 356
susceptibility to, 465–467
toxicity of, 357
Vps51 protein
of Candida albicans, 262
in invasion, 273
Vulvar vestibulitis syndrome
recurrent, 423
Vulvovaginal candidiasis
animal models for, 143, 145
biofilms in, 146
complicated, 424
drugs for, 421, 424
epidemiology of, 420
gene expression in, 287
incidence of, 145, 387–388
microbiology of, 420, 422–423
natural history of, 144
pathogenesis of, 420, 422–423
pathophysiology of, 155
recurrent, 145, 162, 172
risk factors for, 145, 172, 422–423
species causing, 11–12
treatment of, 424
vaccines for, 172
W
Wap proteins
in cell wall, 205
Weak acid stress response, 228–229
Wh11 protein
in mating, 84
in switching, 81
White cells, see also Switching
in mating, 76–78
White-opaque switch, Candida albicans,
15
Whole-genome duplication, in cell cycle,
110
Wildlife, strain variation found in, 95
Wor proteins, in switching, 82–83, 104
Wpre protein, in mating, 84
X
Xanthomonas campestris, Candida albicans
Y
Yak1 protein, in biofilm formation, 302,
306
Yap proteins
Yapsins, 213
Yarrowia lipolytica
cell wall of, 209
cyclins of, 110
Yck proteins, in invasion, 288
Yeast cells, morphology of, 101–103,
299–300
Yeast Gene Order Browser, 38
Ygb proteins, in liver lesions, 293
YHB1 protein, in histatin response, 190
Yhb proteins
in invasion, 288
in nitrosative stress response, 228
Yku protein, in DNA repair, 64
Yps7 protein, in cell wall, 204
YTTYPL tandem repeats, in cell wall, 210
Ywp1 protein, in biofilm formation, 302,
303–304
Z
Zap proteins, in biofilm formation, 302,
307
Zinc, stress response to, 229
Zygomycetes, antifungal drugs for, 349

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