Los días 7 y 8 de mayo organizamos en la Fundación Ramón Areces con la Fundación General CSIC el Simposio Internacional 'Microbiología: transmisión'. La "transmisión" en microbiología hace referencia al proceso por el que material genético es transferido de una célula a otra, de una población a otra. Es un proceso clave para entender el origen y la evolución de los seres vivos. El objetivo de esta reunión era conocer mejor la logística de la transmisión para ser capaces de modular o suprimir algunos procesos de transmisión dañinos.
Functional Genomics of Plant Pathogen interactions in Wheat Rust PathosystemSenthil Natesan
Cereal rust fungi are pathogens of major importance to agriculture, threatening cereal production worldwide. Targeted breeding for resistance, based on information from fungal surveys and population structure analyses of virulence, has been effective. Nevertheless, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to determine the range of available resistance genes. The development of genomic resources for these fungi and their comparison has released a torrent of new ideas and approaches to use this information to assist pathologists and agriculture in general. The sequencing of gene transcripts and the analysis of proteins from haustoria has yielded candidate virulence factors among which could be defence-triggering avirulence genes. Genome-wide computational analyses, including genetic mapping and transcript analyses by RNA sequencing of many fungal isolates, will predict many more candidates (Bakkeren et al., 2012)
Dissecting the mechanisms of host-pathogen systems like wheat-rust, including pathogen counter-defenses will ensure a step ahead towards understanding current outcomes of interactions from a co-evolutionary point of view, and eventually move a step forward in building more durable strategies for management of diseases caused by fungi (Hadrami et al.,2012)
The power point presentation includes information regarding various methods and concepts involved in fungi bacteria and virus with some suitable examples
Gene for gene system in plant fungus interactionVinod Upadhyay
MOLECULAR CHARACTERIZATION OF GENE FOR GENE SYSTEMS IN PLANT- FUNGUS INTERACTION AND THE APPLICATIONS OF AVIRULENCE GENES IN CONTROL OF PLANT PATHOGENS
Molecular basis of plant resistance and defense responses to pathogensSenthil Natesan
In response to pathogen attack, plants have evolved sophisticated defense mechanisms to delay or arrest pathogen growth.Unlike animals, plants lack a circulating immune system recognizing microbial pathogens. Plant cells are more autonomous in their defense mechanisms and rely on the innate immune capacity of each cell and systemic signals that disseminate from infection sites (Jones and Dangl, 2006). Plant innate immunity consists of preformed physical and chemical barriers (such as leaf hairs, rigid cell walls, pre-existing antimicrobial compounds) and induced defenses. Should an invading microbe successfully breach the pre-formed barriers, it may be recognized by the plant, resulting in the activation of cellular defense responses that stop or restrict further development of the invader.
Functional Genomics of Plant Pathogen interactions in Wheat Rust PathosystemSenthil Natesan
Cereal rust fungi are pathogens of major importance to agriculture, threatening cereal production worldwide. Targeted breeding for resistance, based on information from fungal surveys and population structure analyses of virulence, has been effective. Nevertheless, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to determine the range of available resistance genes. The development of genomic resources for these fungi and their comparison has released a torrent of new ideas and approaches to use this information to assist pathologists and agriculture in general. The sequencing of gene transcripts and the analysis of proteins from haustoria has yielded candidate virulence factors among which could be defence-triggering avirulence genes. Genome-wide computational analyses, including genetic mapping and transcript analyses by RNA sequencing of many fungal isolates, will predict many more candidates (Bakkeren et al., 2012)
Dissecting the mechanisms of host-pathogen systems like wheat-rust, including pathogen counter-defenses will ensure a step ahead towards understanding current outcomes of interactions from a co-evolutionary point of view, and eventually move a step forward in building more durable strategies for management of diseases caused by fungi (Hadrami et al.,2012)
The power point presentation includes information regarding various methods and concepts involved in fungi bacteria and virus with some suitable examples
Gene for gene system in plant fungus interactionVinod Upadhyay
MOLECULAR CHARACTERIZATION OF GENE FOR GENE SYSTEMS IN PLANT- FUNGUS INTERACTION AND THE APPLICATIONS OF AVIRULENCE GENES IN CONTROL OF PLANT PATHOGENS
Molecular basis of plant resistance and defense responses to pathogensSenthil Natesan
In response to pathogen attack, plants have evolved sophisticated defense mechanisms to delay or arrest pathogen growth.Unlike animals, plants lack a circulating immune system recognizing microbial pathogens. Plant cells are more autonomous in their defense mechanisms and rely on the innate immune capacity of each cell and systemic signals that disseminate from infection sites (Jones and Dangl, 2006). Plant innate immunity consists of preformed physical and chemical barriers (such as leaf hairs, rigid cell walls, pre-existing antimicrobial compounds) and induced defenses. Should an invading microbe successfully breach the pre-formed barriers, it may be recognized by the plant, resulting in the activation of cellular defense responses that stop or restrict further development of the invader.
Host-pathogen Interactions, Molecular Basis and Host Defense: Pathogen Detect...QIAGEN
Host–pathogen interactions are strikingly complex during infection. This slidedeck provides an overview of the molecular basis of these intricate interactions: the impact of microbiota on innate and adaptive immunity, metabolism, and insulin resistance and host defense mechanisms. Various research tools will be introduced to simplify and streamline each step of studying the host response, enabling detection of pathogens, analysis of gene expression and regulation, epigenetic modification, genotyping and signal transduction pathway activation.
The study of pathogenomics attempts to utilize genomic and metagenomics data gathered from high through-put technologies to understand microbe diversity and interaction as well as host-microbe interactions involved in causing the disease. Pathogenomics researchers are generating and analyzing genome sequences of diverse bacterial, oomycete, fungal and viral pathogens to identify genetic sources of virulence, understand differences observed among related pathogens, guide the development of diagnosis tools capable of discriminating among specific strains, reveal sources of host resistance and understand the dynamics of host-microbe interactions and the diseases they cause .
The concept of gene for gene hypothesis was first developed by Flor in 1956 based on his studies of host pathogen interaction in flax, for rust caused by Melampsora lini. The gene for gene hypothesis states that for each gene controlling resistance in the host, there is corresponding gene controlling pathogenicity in the pathogen. The resistance of host is governed by dominant genes and virulence of pathogen by recessive genes. The genotype of host and pathogen determine the disease reaction. When genes in host and pathogen match for all loci, then only the host will show susceptible reaction. If some gene loci remain unmatched, the host will show resistant reaction. Now gene – for –gene relationship has been reported in several other crops like potato, sorghum, wheat, etc. The gene for gene hypothesis is also known as “Flor Hypothesis.”
this is a review about evolution of antibiotic resistance. I tried to answer how bacteria acquire new genes to resist, how they choose, what are people doing to prevent this increasing resistance levels.
genetic Resistance against gastrointestinal nematodes in sheep: Association w...Ishfaq Maqbool
describes briefly about need of breeding for genetic resistance, candidate genes associated with resistance, genomic regions located on different sheep chromosomes and mechanisms by which the genes act.
Fernando Vaquero-El impacto de las ciencias ómicas en la medicina, la nutrici...Fundación Ramón Areces
El 29 de marzo de 2016 celebramos un Simposio Internacional sobre el 'Impacto de las ciencias ómicas en la medicina, nutrición y biotecnología'. Organizado por la Fundación Ramón Areces en colaboración con la Real Academia Nacional de Medicina y BioEuroLatina, abordó cómo un mejor conocimiento del genoma humano está permitiendo notables avances hacia una medicina de precisión.
Host-pathogen Interactions, Molecular Basis and Host Defense: Pathogen Detect...QIAGEN
Host–pathogen interactions are strikingly complex during infection. This slidedeck provides an overview of the molecular basis of these intricate interactions: the impact of microbiota on innate and adaptive immunity, metabolism, and insulin resistance and host defense mechanisms. Various research tools will be introduced to simplify and streamline each step of studying the host response, enabling detection of pathogens, analysis of gene expression and regulation, epigenetic modification, genotyping and signal transduction pathway activation.
The study of pathogenomics attempts to utilize genomic and metagenomics data gathered from high through-put technologies to understand microbe diversity and interaction as well as host-microbe interactions involved in causing the disease. Pathogenomics researchers are generating and analyzing genome sequences of diverse bacterial, oomycete, fungal and viral pathogens to identify genetic sources of virulence, understand differences observed among related pathogens, guide the development of diagnosis tools capable of discriminating among specific strains, reveal sources of host resistance and understand the dynamics of host-microbe interactions and the diseases they cause .
The concept of gene for gene hypothesis was first developed by Flor in 1956 based on his studies of host pathogen interaction in flax, for rust caused by Melampsora lini. The gene for gene hypothesis states that for each gene controlling resistance in the host, there is corresponding gene controlling pathogenicity in the pathogen. The resistance of host is governed by dominant genes and virulence of pathogen by recessive genes. The genotype of host and pathogen determine the disease reaction. When genes in host and pathogen match for all loci, then only the host will show susceptible reaction. If some gene loci remain unmatched, the host will show resistant reaction. Now gene – for –gene relationship has been reported in several other crops like potato, sorghum, wheat, etc. The gene for gene hypothesis is also known as “Flor Hypothesis.”
this is a review about evolution of antibiotic resistance. I tried to answer how bacteria acquire new genes to resist, how they choose, what are people doing to prevent this increasing resistance levels.
genetic Resistance against gastrointestinal nematodes in sheep: Association w...Ishfaq Maqbool
describes briefly about need of breeding for genetic resistance, candidate genes associated with resistance, genomic regions located on different sheep chromosomes and mechanisms by which the genes act.
Fernando Vaquero-El impacto de las ciencias ómicas en la medicina, la nutrici...Fundación Ramón Areces
El 29 de marzo de 2016 celebramos un Simposio Internacional sobre el 'Impacto de las ciencias ómicas en la medicina, nutrición y biotecnología'. Organizado por la Fundación Ramón Areces en colaboración con la Real Academia Nacional de Medicina y BioEuroLatina, abordó cómo un mejor conocimiento del genoma humano está permitiendo notables avances hacia una medicina de precisión.
Silkworm has developed an efficient host defense mechanism against invading microorganisms through their immunological and genetic resistance. Immunological responses in silkworm B.mori are provided by circulating haemocytes which play an important role in innate immune mechanism such as phagocytosis, cellular encapsulation, phenoloxidase cascade and synthesis of antimicrobial proteins which are effectively engaged in defense reactions against invading pathogens . Antimicrobial proteins are the armament that insects have developed to fight off the pathogens. Several such antimicrobial proteins have been reported from silkworm B.mori like cecropins, attacins, lebocin, moricin, gloverins, lysozyme, defensins and hemolin. Insects in general are observed to respond differentially to infection by pathogens. Such differences are genetically determined and have been extensively studied in silkworm to develop resistant breeds.
virulence of plant pathogenic bacteria.pptxReddykumarAv
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host.[1] The pathogenicity of an organism—its ability to cause disease—is determined by its virulence factors.[2][3] In the specific context of gene for gene systems, often in plants, virulence refers to a pathogen's ability to infect a resistant host.
Jordi Torren - Coordinador del proyecto ESVAC. Agencia Europea de Medicamento...Fundación Ramón Areces
El martes 5 de junio del 2018 organizamos una Jornada en la Fundación Ramón Areces, en la cual se habló sobre el consumo de antibióticos y transmisión de resistencia entre humanos y animales.
Dominique L. Monnet Director del programa ARHAI (Antimicrobial Resistance an...Fundación Ramón Areces
El martes 5 de junio del 2018 organizamos una Jornada en la Fundación Ramón Areces, en la cual se habló sobre el consumo de antibióticos y transmisión de resistencia entre humanos y animales.
El jueves 24 de mayo del 2018 organizamos una Conferencia con Antonio Cabrales en la Fundación Ramón Areces. Una conferencia en la cual el tema fue: Estilo negociador y confianza, ¿hay diferencias entre hombres y mujeres?
Teresa Puig - Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Espa...Fundación Ramón Areces
El lunes y martes 21 y 22 de mayo del 2018 realizamos un Simposio Internacional en la Fundación Ramón Areces, tratando el tema de la superconductividad y presión: una relación fructífera en el camino hacia la superconductividad a temperatura ambiente.
Elena Bascones - Instituto de Ciencia de Materiales de Madrid (ICMM-CSIC), Es...Fundación Ramón Areces
El lunes y martes 21 y 22 de mayo del 2018 realizamos un Simposio Internacional en la Fundación Ramón Areces, tratando el tema de la superconductividad y presión: una relación fructífera en el camino hacia la superconductividad a temperatura ambiente.
El jueves 17 de mayo del 2018 se organizó una Mesa Redonda en la Fundación Ramón Areces, en la cual se habló sobre las subidas de tipos en la era Trump y la nueva globalización.
El jueves 17 de mayo del 2018 se organizó una Mesa Redonda en la Fundación Ramón Areces, en la cual se habló sobre las subidas de tipos en la era Trump y la nueva globalización.
El miércoles 16 de mayo del 2018 celebramos una Jornada en la Fundación Ramón Areces, en la cual se habló sobre las nuevas fronteras de investigación sobre la distribución comercial y el comportamiento del consumidor.
El miércoles 16 de mayo del 2018 celebramos una Jornada en la Fundación Ramón Areces, en la cual se habló sobre las nuevas fronteras de investigación sobre la distribución comercial y el comportamiento del consumidor.
Juan Carlos López-Gutiérrez - Unidad de Anomalías Vasculares, Hospital Unive...Fundación Ramón Areces
El jueves y viernes 10 y 11 de mayo del 2018 realizamos en la Fundación Ramón Areces un Simposio Internacional, en el cual se trató el tema del mosaicismo somático en malformaciones vasculares.
Víctor Martínez-Glez. - Instituto de Genética Médica y Molecular (INGEMM). I...Fundación Ramón Areces
El jueves y viernes 10 y 11 de mayo del 2018 realizamos en la Fundación Ramón Areces un Simposio Internacional, en el cual se trató el tema del mosaicismo somático en malformaciones vasculares.
Rudolf Happle - Dermatología, University of Freiburg Medical Center, Freiburg...Fundación Ramón Areces
El jueves y viernes 10 y 11 de mayo del 2018 realizamos en la Fundación Ramón Areces un Simposio Internacional, en el cual se trató el tema del mosaicismo somático en malformaciones vasculares.
Rafael Doménech - Responsable de Análisis Macroeconómico, BBVA Research. Fundación Ramón Areces
El martes 8 de mayo de 2018 realizamos una conferencia en la Fundación Ramón Areces, en la cual se habló sobre el futuro de las pensiones: una visión global.
El martes 8 de mayo de 2018 realizamos una conferencia en la Fundación Ramón Areces, en la cual se habló sobre el futuro de las pensiones: una visión global.
El martes 8 de mayo de 2018 realizamos una conferencia en la Fundación Ramón Areces, en la cual se habló sobre el futuro de las pensiones: una visión global.
Nicholas Barr - Profesor de Economía Pública, London School of Economics. Fundación Ramón Areces
El martes 8 de mayo de 2018 realizamos una conferencia en la Fundación Ramón Areces, en la cual se habló sobre el futuro de las pensiones: una visión global.
El viernes 27 de abril del 2018 se celebró en la Fundación Ramón Areces una Jornada sobre física , en la cual se trataron diversos temas como: Los materiales mecanocalóricos, magnetísmo, biofísica, la energía oscura y instrumentación astronómica.
El viernes 20 de abril organizamos una Jornada sobre la ciencia en el corazón de Europa, en colaboración con Científicos Españoles en Bélgica (CEBE) y realizada en la Fundación Ramón Areces.
Marta Olivares - Investigadora Postdoctoral en Université catholique de Louva...Fundación Ramón Areces
El viernes 20 de abril organizamos una Jornada sobre la ciencia en el corazón de Europa, en colaboración con Científicos Españoles en Bélgica (CEBE) y realizada en la Fundación Ramón Areces.
El viernes 20 de abril organizamos una Jornada sobre la ciencia en el corazón de Europa, en colaboración con Científicos Españoles en Bélgica (CEBE) y realizada en la Fundación Ramón Areces.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
2. Ecology and evolution of chromosomal gene transfer between environmental
microorganisms and pathogens: An exaptation tale
3. Horizontal gene transfer is neither a mechanism allowing canonical
step-wise evolution nor sex
Genetic events underlying evolution.
Mutation (including genome rearrangements): Allows stepwise
evolution by producing incremental changes in gene sequences.
Sexual recombination: Allows stepwise evolution by shuffling the
combination of alleles already present in the species
Horizontal gene transfer: Allows the acquisition of a novel trait,
not necessarily present before in the species, as a whole; evolution in
quantum leaps.
4. Martínez, J. L. (2008) Science 321: 365-367.
To pathogenic microparasites (viruses,
bacteria, protozoa, or fungi), we and other
mammals (living organisms at large) are
little more than soft, thin-walled flasks of
culture media.
Levin, B.R. & Antia, R. (2001) Science
292: 1112-1115
Human body is en extreme environmental, which is rich in nutrients
5. In the treated patient, bacteria require
being simultaneously virulent and
resistant to antibiotics
Virulence has evolved along
thousands to hundreds of millions of
years.
Acquired antibiotic resistance is
the product of decades of evoution
The use of antibiotics makes human body an
even more extreme environment
patOP
Picasso
Goya
J.L.Martínez,F.Baquero(2002)ClinicalMicrobiology
Reviews.15:647
Are there common rules in the evolution
towards virulence and resistance?
6. Intrinsic and acquired mechanisms of virulence and resistance
Opportunistic pathogens with an environmental origin can present several
virulence determinants, not acquired by horizontal gene transfer, as well as
antibiotic resistance genes.
7. Origin and dissemination of antibiotic
resistance genes
patOP
Similar situation applies for the
acquisition of virulence
determinants, although the
amplification cycle is less
frequent.
8. Virulence involves the acquisition of sets of
genes allowing adaptation to the new
habitat.
This may produce de-adaptation from the
previous habitat and speciation
9. Origin and dissemination of antibiotic
resistance genes
patOP
Single genes can provide
antibiotic resistance to organisms
that are already adapted for
growing in the human host.
Resistance is not linked to
speciation
10. Common virulence factors
Endotoxin (Lipid A of LPS)
Capsule
Colonization factors (attachment to surfaces)
Production of extracellular matrix that enhances
biofilm formation
Acquisition of growth factors (e.g. Fe)
Antigenic phase variation
Resistance to serum killing
Type III secretion
Toxins
Virulence factors as regular elements of the bacterial physiology
Bacterial structure
Bacterial metabolism
Bacterial defense from host
Bacterial injury to the host
11. Role of virulence factors in natural
ecosystems
patOP
Biofilm for attaching to surfaces, for cooperating and
for avoiding protozoan grazing
Tetrahymena after grazing Listeria. Several,
at the vacuoles have been digested, some
are still intact
P. aeruginosa susceptible to grazing
P. aeruginosa resistant to grazing
Matz,J.,Deines,P.,Jürgens,K.(2002)FEMSMicrobiol.Ecol.(2002)57-65
Biofilm formation is important in chronic infections of surfaces
Alginate overproduction avoids macrophages’ action over P. aeruginosa
12. Virulence determinants can be relevant
for surviving outside the host
patOP
Citotoxicity, is as relevant virulence determinant that can have
evolved to avoid nematodes’ and protozoans’ killing:
Prey/predator relationship in an unicellular world
K aerogenes PAO1
Navas, Cobas, G., López, JA,Talavera, M., Ayala, JA., Martínez, JL.(2007) Proc Natl Acad Sci USA.
104:13728-13731
Non-cytotoxic PAO1 mutant
13. Known functions of antibiotic resistance genes
patOP
Antibiotic inactivating enzymes
Macing,D.R.,Rather,P.N.(1999)FrontBiosci4:132-140
Udou,T.,Mizuguchi,Y.,Wallace,R.J.,Jr.(1989)FEMSMicrobiol.Lett.48:227-230
14. Resistance to antibiotics: Fighting back
Proc. Nat. Acad. Sci. USA Vol. 70 pp. 2276-2280,1973 Aminoglycoside Antibiotic-Inactivating Enzymes
in Actinomycetes Similar to Those Present in Clinical Isolates of Antibiotic-Resistant Bacteria
RAOUL BENVENISTE AND JULIAN DAVIES
The metabolic role of the aminoglycoside-modifying enzymes in actinomycetes is not known. Miller
and Walker have postulated that phosphorylated streptomycin might be important as a metabolic
precursor of streptomycin or to detoxify the antibiotic (7). The enzymes might also be required for
transport of these antibiotics in or out of the cell. Alternatively, they may have nothing to do with
antibiotic biosynthesis and may play a role in another biosynthetic process.
Nothing is known about the origin of R factors. The Watanabe hypothesis (4) provides a simple
molecular mechanism for their origin, but we can only speculate on the environmental and evolutionary
factors that play a role in their formation and maintenance. Their presence does not seem to require
the extensive use of a selective antibiotic environment since Gardner et al. (21) have found R factors in
an "antibiotic virgin population" in the Solomon Islands.
15. Known functions of antibiotic resistance
genes
Chromosomally-encoded aminoglycosides N-acetyltransferases (AAC)
Aminoglycoside-inactivating enzymes are classical antibiotic resistance
genes acquired through horizontal gene transfer.
However, several bacterial species that do not produce antibiotics
contain in their chromosomes genes encoding AACs that have not
recently acquired through horizontal gene transfer.
Examples: Providencia stuartii, Mycobacterium fortuitum,
Mycobacterium tuberculosis, Serratia marcescens, Acinetobacter
haemolyticus, Enterococccus faecium, Stenotrophomonas maltophilia,…
At least in the case of P. stuartii, the primary function of the
acetyltransferase is the modification of the peptidoglycan.
Macing,D.R.,Rather,P.N.(1999)FrontBiosci4:132-140
Udou,T.,Mizuguchi,Y.,Wallace,R.J.,Jr.(1989)FEMSMicrobiol.Lett.48:227-230
16. Known functions of antibiotic resistance genes
patOP
Multidrug efflux pumps Enzymes involved in bacterial
physiology and capable to
recognize the antibiotic
17. MDR pumps differ to classical antibiotic
resistance genes
Ubiquitously found in all
organisms
Redundandt (several efflux
pumps in a single organism)
Conserved structure
Conserved chromosomal
genes
Wide range of substrates
This suggests that MDR pumps are ancient
elements with relevant roles for bacterial
physiology
patOP
18. Expression of MDR efflux pumps
is usually repressed by local
regulators
SmeT
smeT smeD smeE smeF
19. smeT smeD smeE smeF
Overexpression
Expression of MDR efflux pumps is high in the presence of
effectors. Knowing the effectors provide clues on the
function of MDR pumps
20. SmeT does not bind antibiotics but binds plants
exudates
EMSA
Model
Specific binding SmeT-Inter smeT-D
DNA + Prot
DNA
SmeT functional mechanism
21. Media CFUs/g
0,00E+00
5,00E+08
1,00E+09
1,50E+09
2,00E+09
2,50E+09
3,00E+09
3,50E+09
D457 MBS411 D457R MBS82 GGL199 MBS108
Media
CFUs/g
** **
The deletion of smeE impairs the capability
of S. maltophilia for colonizing plants. Wild-type
smeE-deletion mutant
SmeDEF, which is the most relevant element
contributing to quinolone resistance in S.
maltophilia is involved in the endophytic
colonization of plants’ roots.
García-León, G., Hernández, A., Hernando-Amado, S., Alavi, P., Berg, G., Martinez, J. L. (2014). Applied and
Environmental Microbiology 80: 4559-4565
22. Exaptation as a major force in the evolution
of antibiotic resistance
AR genes acquired by HGT are expressed in
a different genetic context and in the
absence of their specific regulatory
networks. Their solely function is thus
antibiotic resistance
Martínez, J.L. (2009) Philosophical Transactions of the Royal Society B:
Biological Sciences 267: 2521-2530.
27. Founder effect in the establishment of
antibiotic resistance genes
TEM-1 beta-lactamase is the first antibiotic resistance gene described.
Altought several derivatives of TEM-1 (and other plasmid-encoded
betalactamases) are selected in pathogenic bacteria, the number of completely
different plasmidic beta-lactamases is rather low considering the amount of
potential beta-lactamases in environmental bacteria.
T
P
Q
A
XW
Z
L
D P
P
T
P
Q
A
XW
Z
L
D P
P
A
T
P
Q
A
XW
Z
L
D P
P
A
A
A
A A
AA
A
A
T
P
Q
A
XW
Z
L
D P
P
A
A
A
A A
AA
A
A
Å
å
A
a
A A
A
P
α
β
τ
π
ρ
γ
φ
1 2 3 4
Martínez, J.L., Fajardo, A., Garmendia, L., Hernández, A., Linares, J. F., Martínez-Solano, L., Sánchez,
M. B. (2009) FEMS Microbiology Reviews 33: 44-65
This may also happen for virulence factors: once a T3SS has been
acquired another one would not be needed
29. 1
23
45
6
a
b
c
d
e
f
a
b
Fitness costs associated to antibiotic
resistance
Antibiotic resistance may produce a burden on
bacterial metabolism because:
- Target proteins are very important for bacterial
physiology, so that antibiotic resistance mutations in
this proteins make them less proficient.
-The acquisition of a antibiotic resistance plasmid
renders a metabolic cost (replication, transcription,
translation).
However:
-Some resistance mutations produce no-cost
-Resistant mutants can acquire compensatory
mutations.
-The effect of resistance on bacterial competitivity is
dependant on the ecosystem.
-Systems of co-selection and plasmid stabilization allow
persistence of resistance.
-Metabolic rewiring can compensate fitness costs
Does it also apply for virulence ?
30. Marie Doyle et al. Science 2007;315:251-252
Differential fitness costs of virulence determinants
31. Published by AAAS
The paradoxical efect of H-NS on fitness costs:
Epigenetic effects and expression levels
Marie Doyle et al. Science 2007;315:251-252
32. Marie Doyle et al. Science 2007;315:251-252
High fitness costs of virulence determinants may imply speciation
Driver of speciation
33.
34. Entering in a new host implies global changes in the physiology
35. Dongsheng Zhou, and Ruifu Yang Infect. Immun. 2009;77:2242-
2250
Entering in a new host implies global changes in the physiology: and
consequently in the regulatory networks
36. Evolution of bacterial pathogens: from natural ecosystems to
human hosts
Environmental Microbiology
Volume 15, Issue 2, pages 325-333, 1 AUG 2012 DOI: 10.1111/j.1462-2920.2012.02837.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1462-2920.2012.02837.x/full#f2
37. Evolution of bacterial pathogens: from natural ecosystems to
human hosts
Environmental Microbiology
Volume 15, Issue 2, pages 325-333, 1 AUG 2012 DOI: 10.1111/j.1462-2920.2012.02837.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1462-2920.2012.02837.x/full#f2
Differing to other processes of
recombination-driven evolution (sex), in
which the better adapted offspring
usually outcompete the ancestor. HGT
allows the colonization of a new habitat;
the ancestor can remain and is not
outcompeted by the evolved offspring.
38. patOP
Towards an integrated and ecological view
on bacterial virulence and resistance
Pathogens have acquired virulence traits and
resistance genes out of clinical settings.
Antibiotic resistance genes and virulence
determinants have a relevant ecological role out of
humans.
Infection is a way of gaining access to new niches
and food resources.
Virulence and resistance should have a
metabolic control.
Magritte
41. Crc (Catabolic carbon repression): Global
regulator of resistance and virulence?
Virulence (and resistance) is under metabolic
control
Morales,G.,Linares,J.F.,Beloso,A.,Albar,J.P.Martínez,J.L.,Rojo,F.
(2004).JournalofBacteriology186:1337-1344
crcwt
42. Effect of Crc on the
virulence of P.
aeruginosa
Gene TIGR
Locus
Average
Ratio*
Protein name Main role Reported role in virulence or resistance Putative Crc-binding sequence
and position (relative to AUG)
hcp1 PA0085 -12.26 Conserved hypothe tical
protein
Type VI secreted effector Type VI secretion (Mougous et al., 2006)
tolB PA0972 -1.5 Transport of small molecules
PA1459 -2.39 Probable
methyltransferase
Chemotaxis and motility Likely swarming** (Yeung et al., 2009).
Susceptibility to several antibiotics
(Dotsch et al., 2009)
gltA PA1580 -1.78 Citrate synthase Energy metabolism Type III Secretion (Rietsch and
Mekalanos, 2006)
fabB PA1609 -1.71 Beta-ketoacyl-ACP
synthase I
Fatty acid and phospholipids
metabolism
tig PA1800 -1.59 Trigger factor Cell division, chaperones & heat
shock proteins
Resistance to quinolones (Breidenstein et
al., 2008)
hcnB PA2194 -1.52 Hydrogen cyani de
synthase HcnB
Central intermediary
metabolism. Biosynthe sis of
cyanide
Cyanide production (Ramette et al.,
2003). Susceptibility to several
antibiotics (Fajardo et al., 2008).
lpxA PA3644 -2.1 UDP-N-
acetylglucosamine
acyltransferase
Cell wall / LPS / capsule
fabZ PA3645 -1.78 (3R)-
Hydroxymyristoyl -[acyl
carrier protein]
dehydratase
Cell wall / LPS / capsule
pepA PA3831 -2.06 Leucine
aminopeptidase
Protein fate Cytotoxicity (Hauser et al., 1998).
Susceptibility to several antibiotics
(Dotsch et al., 2009). Alginate
(Woolwine and Wozn iak, 1999)
murC PA4411 -1.53 UDP-N-
acetylmuramate--
alanine ligase
Cell wall / LPS / capsule Peptidoglycan (Azzolina et al., 2001)
azu PA4922 -3 Azurin precursor Energy metabolism Cytotoxicity towards macrophages
(Yamada et al., 2002)
rho PA5239 -1.69 Termination factor Rho Transcription, RNA processing
and degradation
Swarming (Yeung et al., 2009)
43. Effect of Crc in the multicellular
behaviour of Pseudomonas
aeruginosa
The Crc mutant:
Is less motile
Forms large clumping structures
Produces more EPS
Attaches more efficiently to surfaces
44.
45. Common virulence factors
Endotoxin (Lipid A of LPS)
Capsule
Antigenic phase variation
Acquisition of growth factors (e.g. Fe)
Resistance to serum killing
Antimicrobial resistance
46. patOP
Towards an integrated and ecological view
on bacterial virulence and resistance
Opportunistic pathogens have acquired virulence
traits and resistance genes out of clinical settings
(although they are acquiring novel antibiotic
resistance genes)
Antibiotic resistance genes and virulence
determinants have a relevant ecological role out of
humans.
Infection is a way of gaining access to new niches
and food resources.
Virulence and resistance should have a
metabolic control.
Magritte
47. Known functions of antibiotic resistance genes
besides resistance
patOP
Elements involved in
detoxification of metabolic
intermediates or
mediating bacterial
comunication.
Enzymes involved in
bacterial physiology and
capable to recognize the
antibiotic
Proteins that modulate
the activity of bacterial
targets
48. What is an antibiotic resistance gene?
A gene that contributes to the intrinsic resistance of a given
species
Its overproduction makes bacteria more resistance
Its absence makes bacteria more susceptible
Mutations in some genes as those coding targets, transporters
or regulators can confer resistance; but such genes are not
resistance genes because they will not confer resistance upon
transfer to a heterologous host. There are exceptions as the S.
pneumoniae topoisomerasesA gene that confers resistance upon its transfer to another wild-type bacterial
host
Given that the original function of several resistance genes is not antibiotic
resistance, inferring function by homology is risky
Technical definition
49. Martinez, J. L., F. Baquero & D. I. Andersson, (2007) Predicting antibiotic resistance. Nature Reviews in
Microbiology 5: 958-965.
Martinez, J. L., F. Baquero & D. I. Andersson, (2011) Beyond serial passages: new methods for predicting the
emergence of resistance to novel antibiotics. Curr Opin Pharmacol 11: 439-445.
Functional and sequence-based metagenomics
Functional analysis of comprehensive transposon-tagged
mutants
Molecular epidemiology
Whole-genome-sequence of
antibiotic resistant mutants
Conceptual framework for predicting acquisition of
antibiotic resistance by bacterial pathogens
50. Conceptual framework for predicting antibiotic
resistance
Martinez, J. L., F. Baquero & D. I. Andersson, (2007) Predicting antibiotic resistance. Nature Reviews in
Microbiology 5: 958-965.
Martinez, J. L., F. Baquero & D. I. Andersson, (2011) Beyond serial passages: new methods for predicting the
emergence of resistance to novel antibiotics. Curr Opin Pharmacol 11: 439-445.
56. Fitness costs in the presence of antibiotics: Antibiotic pollution favours
resistance even at non-inhibitory concentrations
57.
58. In the treated patient, bacteria require
being simultaneously virulent and
resistant to antibiotics
To understand in full the infective
process in an antibiotic-overloaded
word, we need to understand the
networks connecting resistance and
virulence
patOP
Picasso
Goya
J.L.Martínez,F.Baquero(2002)ClinicalMicrobiology
If virulence is a way of gaining
access to the resources of a
given ecosystem, it has to be
under metabolic control
60. Fitness cost of different qnr genes
Acquisition of Smqnr of S. maltophila has a fitness cost, which is not
observed in a ∆hns strain
KZM120 (∆acrAB) MC4100 JMG100 (∆hns)
0
20
40
60
80
100
120
pGEM-T
pBS3.25 pBS18 pBS19 pBS20
Cellswithplasmid(%)
Smqnr qnrA1 qnrA3 qnrA4
Escherichia coli
61. Mutations take place in the chromosome of Escherichia coli
Stability of pBS3.25 after evolution
No mutations in the plasmid
E. coli KZM120 pBS3.25
evol
0
20
40
60
80
100
120
pGEM-T MBS25 MBS228 MBS229 MBS230 MBS231
retr
Cellswithplasmid(%)
(A) The directed network of recent lateral gene transfers. Node color corresponds to the taxonomic group of donors and recipients listed at the bottom. Connected components of endosymbionts are marked with numbers: (1) Helicobacter, (2) Coxiella, (3) Bartonella, (4) Leptospira, (5) Legionella, (6) Ehrlichia. Clusters of cyanobacteria are marked with letters: (a) high-light adapted Prochlorococcus, (b) low-light adapted Prochlorococcus, (c) marine Synechococcus, (d) other Synechococcus, (e) Nostocales and Chroococcales. Enlarged images of clusters (right) are marked with asterisks. Species names are written by the vertices. Annotations of transferred genes appear next to the edges. (B) Community structure within the largest connected component of the dLGT network (for the entire network, see Supplemental Fig. S2). Vertices that are grouped into the same module are colored the same. (C) Pathogens in the largest connected component of the dLGT network (for the entire network, see Supplemental Fig. S6). The arrow marks a nonpathogen (Bukholderia thailandensis) within a pathogenic community.
The effect of plasmids pSf-R27 and pSf-R27Δsfh on bacterial host survival in J774-A.1 macrophage. J774-A.1 macrophage–like cells were infected with SL1344, SL1344 (pSf-R27), or SL1344 (pSf-R27Δsfh) as described in supporting online material. Bacteria were recovered at the time intervals shown, and the number of colony-forming units of each bacterial strain was determined.
The impact of plasmids pSf-R27 and pSf-R27Δsfh on the transcriptome of SL1344. Data are presented for exponential (white bars) and stationary-phase (black bars) microarray data from SL1344 versus SL1344 (pSf-R27) (A) and SL1344 (pSf-R27) versus SL1344 (pSf-R27Δsfh) (B). Gene categories are given at the left of each panel and are based on the Kyoto Encyclopedia of Genes and Genomics (KEGG). The histograms represent the percentage of genes in each category affected by the introduction of the plasmid.
The effect of plasmids pSf-R27 and pSf-R27Δsfh on bacterial host survival in J774-A.1 macrophage. J774-A.1 macrophage–like cells were infected with SL1344, SL1344 (pSf-R27), or SL1344 (pSf-R27Δsfh) as described in supporting online material. Bacteria were recovered at the time intervals shown, and the number of colony-forming units of each bacterial strain was determined.
Remodeling of gene regulation in Y. pestis and Y. pseudotuberculosis. Transcription regulators listed here bind to cis-acting DNA sequences within the promoters of their target genes and either activate or repress transcription initiation of these targets. Some regulators (e.g., CRP) can function as either activators or repressors according to the target promoters. Shown also is autoregulation of some regulators (e.g., RovA).