16. R. Villano “Superbugs & Superdrugs”, You plot historical notes on the concept of antibiosis, on research, discovery and production of antibiotics and their global role not only therapeutic but also strategic since World War II. Then, you look at national and international issues related consumption, misuse and overuse of antibiotics in humans, in animal husbandry, agriculture, and thus in the food chain and the environment; policies to combat the phenomenon of excessive prescription and citizens in the degree of information and awareness of the risks; guidelines of good practice behavior of the patient; the main documents of struggle in this emergency. We make also an analytical overview and a discussion of some super diseases (tuberculosis, gonorrhea, meningitis, etc.) And bacterial resistance to major antibiotics. We realize, finally, a survey on current technologies and addresses of applied research and a survey on major recent new therapies. Closes work a technical appendix containing an apparatus essential regulations and ministerial directives Italian and European Community on the theme. (Chiron dpt Praxys, Roma, June 2015, pp. 256);

1. Raimondo Villano
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2. Raimondo Villano
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3. Superbugs & Superdrugs
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Contents index
Sommario 13
Abstract 15
Résumé 17
Abstrakt 19
Abstracto 21
1. A brief history of antibiotics 25
2. Issues and contrast of antibiotic 33
3. Major resistance to antibiotics 49
4. Look back at some super diseases 55
5. Technologies and research directions 65
6. New therapeutic compounds 77
7. Appendix 85
8. Author profile 169

5. Raimondo Villano
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“Life is short, art is long,
the favorable opportunity,
attempting misleading,
the difficult decision”
Hippocrates

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Parole chiave
antibiotici, resistenza, batteri.
Keywords
antibiotics, resistance, bacteria.
Classification LCC
RM 265 - 267.
Title
Antibiotic resistance.

7. Raimondo Villano
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Sommario
Si tracciano cenni storici sul concetto di antibiosi, su ricerche, scoperta e
produzione degli antibiotici e sul loro ruolo mondiale non solo terapeutico
ma anche strategico dal secondo dopoguerra. Poi, si esaminano a livello
nazionale ed internazionale: le problematiche inerenti consumo, uso
improprio e abuso di antibiotici nell’uomo, in zootecnia, agricoltura e,
quindi, nel ciclo alimentare e nell’ambiente; le politiche di contrasto al
fenomeno dell’iperprescrizione e nei cittadini il grado di informazione e
consapevolezza dei rischi; le linee guida di buona prassi comportamentale
del malato; i documenti principali di lotta a tale emergenza. Si effettuano,
inoltre, una rassegna analitica e un approfondimento su alcune super
patologie (tubercolosi, gonorrea, meningite, ecc.) e sulle resistenze
batteriche ai principali antibiotici. Si realizzano, infine, una ricognizione
sull’attualità delle tecnologie e degli indirizzi di ricerca applicata e una
rassegna sulle principali recenti nuove terapie. Chiude il lavoro
un’appendice tecnica contenente un apparato essenziale di normative e
direttive ministeriali italiane e comunitarie europee sul tema.

8. Raimondo Villano
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Abstract
You plot historical notes on the concept of antibiosis, on research,
discovery and production of antibiotics and their global role not only
therapeutic but also strategic since World War II. Then, you look at
national and international issues related consumption, misuse and overuse
of antibiotics in humans, in animal husbandry, agriculture, and thus in the
food chain and the environment; policies to combat the phenomenon of
excessive prescription and citizens in the degree of information and
awareness of the risks; guidelines of good practice behavior of the patient;
the main documents of struggle in this emergency. We make also an
analytical overview and a discussion of some super diseases (tuberculosis,
gonorrhea, meningitis, etc.) And bacterial resistance to major antibiotics.
We realize, finally, a survey on current technologies and addresses of
applied research and a survey on major recent new therapies. Closes work
a technical appendix containing an apparatus essential regulations and
ministerial directives Italian and European Community on the theme.

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Résumé
Vous tracez notes historiques sur le concept de antibiose, sur la recherche,
la découverte et la production d’antibiotiques et de leur rôle dans le monde
non seulement thérapeutique, mais aussi stratégique depuis la Seconde
Guerre mondiale. Ensuite, vous regardez les questions nationales et
internationales liées à la consommation, utilisation abusive et excessive
d’antibiotiques chez l’homme, dans l'élevage, l'agriculture et, donc, dans la
chaîne alimentaire et l’environnement; politiques de lutte contre le
phénomène de la prescription excessive et les citoyens dans le degré
d’information et de sensibilisation des risques; lignes directrices de bonne
conduite de la pratique du patient; les principaux documents de lutte dans
cette situation d’urgence. Nous faisons également un aperçu analytique et
une discussion de certaines super maladies (tuberculose, la gonorrhée, la
méningite, etc.) et de la résistance bactérienne aux antibiotiques majeurs.
Nous nous rendons compte, enfin, une enquête sur les technologies et les
adresses de la recherche appliquée en cours et une enquête sur les
principales nouvelles thérapies récentes. Ferme fonctionne une annexe
technique contenant les règlements essentiels de l’appareil et les directives
ministérielles italiennes et de la Communauté européenne sur le thème.

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Abstrakt
Sie plotten historische Anmerkungen über das Konzept der Antibiose, auf
Forschung, Entdeckung und Herstellung von Antibiotika und ihre Rolle in
der Welt nicht nur therapeutisch, sondern auch strategische dem Zweiten
Weltkrieg. Dann schauen Sie auf nationalen und internationalen Fragen im
Zusammenhang mit Konsum, Missbrauch und übermäßige Einsatz von
Antibiotika bei Menschen, in der Tierhaltung, Landwirtschaft, und damit in
die Nahrungskette und die Umwelt; Politik zur Bekämpfung des
Phänomens die übermäßige Verschreibung und Bürger in den Grad der
Information und Sensibilisierung der Risiken; Leitlinien für die gute Praxis
Verhalten des Patienten; die wichtigsten Dokumente des Kampfes in
diesem Notfall. Wir machen auch einen analytischen Überblick und eine
Diskussion einiger Super Krankheiten (Tuberkulose, Gonorrhö, Meningitis,
etc.) und bakterieller Resistenz gegen wichtige Antibiotika. Wir wissen,
schließlich eine Umfrage zu aktuellen Technologien und Adressen von
angewandter Forschung und eine Umfrage zu den wichtigsten aktuellen
neuen Therapien. Schließt Arbeit eine technische Anlage, die eine
Vorrichtung wesentliche Vorschriften und Ministerialrichtlinien
italienischen und europäischen Gemeinschaft über das Thema.

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Abstracto
Trazar notas históricas sobre el concepto de antibiosis, en la investigación,
el descubrimiento y la producción de antibióticos y su papel global no sólo
terapéutico, sino también estratégico desde la Segunda Guerra Mundial. A
continuación, nos fijamos en los asuntos nacionales e internacionales
relacionados con el consumo, el mal uso y abuso de los antibióticos en los
seres humanos, en la ganadería, la agricultura, y por lo tanto en la cadena
alimentaria y el medio ambiente; políticas de lucha contra el fenómeno de
la prescriptión excesiva y los ciudadanos en el grado de información y
conocimiento de los riesgos; pautas de comportamiento de buenas
prácticas de la paciente; los principales documentos de lucha en esta
emergencia. Hacemos también un resumen analítico y una discusión de
algunas enfermedades súper (tuberculosis, gonorrea, meningitis, etc.) y la
resistencia bacteriana a los principales antibióticos. Nos damos cuenta,
por último, un estudio sobre las tecnologías y las direcciones de la
investigación aplicada en curso y una encuesta sobre las principales
nuevas terapias recientes. Cierra funciona un anexo técnico que contiene
un aparato regulaciones esenciales y directivas ministeriales italianas y de
la Comunidad Europea sobre el tema.

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S U P E R B U G S & S U P E R D R U G S

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5. Technologies and research directions

14. Superbugs & Superdrugs
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15. Raimondo Villano
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Rapid changes are needed to avoid the misery and death of a potential
"post-antibiotic era".
The solutions appear to be the contrast of the emergency, the monitoring of
cases of resistance to infection prevention to reduce the need for antibiotics
upstream through improved hygiene, access to cleaner water,
immunizations, infection control structures health. That the super-bacteria
must be a war of alliances, in which all can and must do their part.
In many instances the available diagnostic tests can already be used to
identify bacteria that feed an infection, allowing doctors to choose
pharmacological treatments more targeted instead of resorting to drugs
broad spectrum which aggravate the resistance. The problem, though, is
that these tests take time and doctors will often give up resorting to broad-
spectrum antibiotics.
According to the EU report, test development faster is crucial(75)
.
It can also be very useful a renewed focus and standardized methods for
monitoring of resistant strains worldwide.
Currently there is no global consensus on the methodology and data
collection in this area.
There are also daily practices essential that communities and clinicians
should adopt, including better hygiene for health care, such as washing
hands frequently, and vaccinate the population against key diseases to
reduce the need to antibiotics(76)
.
The acceleration of the development of bacterial resistance to antibiotics,
then, would be precisely correlated with more aggressive antibiotic
therapy: a contradiction is only apparent, it came to light thanks to an
experiment of Escherichia coli.
According to a study, the bacteria survived a massive use of medicines are
benefited by the lack of competition with other bacteria susceptible to
antibiotics(77)
.
So, the more powerful antibiotic treatment, the faster the bacteria develop
resistance to these drugs.
______________
(75) Dina Fine Maron, Ibid.
(76) Dina Fine Maron, Ibid.
(77) Scientific American, Antibiotic resistance, a look to genetics, (from a study
published in 'PLoS Biology' by Robert Beardmore and colleagues, a group of
microbiologists from the University of Exeter in the UK, in collaboration with
colleagues at the University Kiel, Germany), April 4, 2013.

16. Superbugs & Superdrugs
68
These therapies fact eliminate the bacteria are not resistant, thus resulting
in a lack of competition that enables those resistant to multiply quickly.
The result provides an explanation for the microbiological resistance to
antibiotics of specific subpopulations of bacteria that survive after being
exposed to molecules that should eliminate them.
In the study there was a very powerful genetic mechanism of defense
deployed by E. coli, which produces fast copies of genes that confer
resistance, reducing the effectiveness of the medication abruptly. The result
was confirmed by mathematical models and sequencing the entire genome
of strains resistant and non-resistant bacterium. "It is amazing how quickly
the bacteria develop resistance: were even stopped the experiments,
considering that the treatments would not lose their effectiveness quickly,
even within a day(78)
."
It was possible to know, however, "that the bacteria survived after initial
treatment have duplicated their specific areas of the genome that contain
many genes that confer resistance to antibiotics. The expression of these
genes seems faster when antibiotics are combined, with the result of a rapid
evolution of bacteria very resistant(79)
".
The survival to antibiotics remaining in a state of relative quiescence until
the concentration of the drugs is not decreases a capacity of the bacteria
that develops before the evolution of resistance, favoring the onset(80)
. The
discovery of the mechanisms behind this phenomenon of tolerance opens
the way to new strategies to prevent the spread of drug-resistant bacteria(81)
.
The mechanism at the basis of so-called bacterial tolerance, ie the ability of
bacteria to survive the aggression of antibiotics using a different strategy,
and in some aspects more efficient, the development of resistance has been
identified by a group of researchers of Hebrew University of Jerusalem(82)
.
The resistance to one or more antibiotics is the ability of a microorganism
to grow even in the constant presence of antibiotic, but on condition that
the concentration of the substance is not too high.
______________
(78) Robert Beardmore.
(79) Robert Beardmore.
(80) The Science, discovered the secret of such susceptibility, June 26, 2014.
(81) The Sciences, Ibid.
(82) Ofer Fridman, Amir Goldberg, Irine Ronin, Noam Shoresh & Nathalie Q. Balaban,
Optimisation of lag time underlies antibiotic tolerance evolved in bacterial populations,
Nature 513, 418-421, 18 September 2014.

17. Raimondo Villano
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The tolerance, however, is the ability to survive until the concentration of
antibiotic decreases; so far these basic mechanisms have been much less
studied.
Following the evolution of populations of E. coli exposed to high
concentrations of ampicillin but intermittent, characterizing the strains that
gradually evolve, it was discovered that the first adaptive change to the
stress from antibiotic that is manifested is precisely the tolerance, which is
presented when there is still no mutation, indicating the development of
resistance (83).
In particular, researchers have found that the tolerance is linked to a
prolonged persistence of the cells in the so-called phase lag (delay phase).
When bacterial cells arrive in a new environment (Petri dish or host
organism), their number does not grow immediately.
The period preceding the beginning of the multiplication, the phase lag in
fact, can last from an hour to a few days, with individual variations in the
microbial population.
Balaban and colleagues have found that bacterial colonies tend to tune the
length of the phase delay of that of the period for which they are exposed to
high doses of antibiotic, to pass to the phase of cell growth (in which they
multiply exponentially) in the periods where administration is interrupted.
With the sequencing of the genome of different strains that had evolved
and by comparison with that of the original strain, the researchers were
then able to identify the gene that controls the length of the delay phase,
which they named tbl (tolerance by lag).
This discovery further draws attention to the importance of proper use of
antibiotics, and offers the opportunity to develop new strategies to prevent
the development of resistance.
Finally, it should be considered the correlation between time of hospital
stay and likelihood of multi-resistant pathogenic outbreaks. In the scientific
community it believes that the probability of getting an infection in the
hospital due to a pathogen (MDR) is directly proportional to the length of
hospitalization.
______________
(83) Balaban et al., Ibid.

18. Superbugs & Superdrugs
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In a study(84)
has looked into this report of 949 cases of documented
infection by Gram negative that occurred between 1998 and 2011. The
ratio of hospital days (from the day of admission to infection), and
probability of infection with MDR Gram negative was examined using
multivariate logistic regression. The MDR was defined as resistance to ≥ 1
drug within ≥ 3 classes of antibiotics.
With + MDR as the dependent variable, the bodies concerned (Escherichia
coli, Enterobacter spp, Pseudomonas aeruginosa, Klebsiella pneumoniae,
etc.) Were included in the final model. The researchers concluded that there
is a strong relationship between time of infection and infection with MDR
pathogens (p = 0.0002). Each day of hospitalization increased the chance of
infection pathogen MDR by an additional 1% (95% CI 1.005 to 1.017).
When they checked the time of infection using K. pneumoniae as a
pathogen of reference, have found that the probability that the Enterobacter
spp. were multiresistant was of 5:57 times higher, while the P. aeruginosa
had 0.44 times less likely to be MDR (95% CI 3.44 to 8.99 and 0.321 to
0.987, respectively). The study concluded that: there is a strong relationship
between time in hospital and time of infection with multidrug-resistant
Gram-negative pathogen, but the strength of this relationship varies
depending on the pathogen; other factors related to the characteristics of the
patients could affect this relationship. These results, therefore, scientists
should be considered when selecting the empirical antibiotic therapy for
these infections. A significant use of search technology can be 4D electron
microscopy, which produces 'movies' of invisible processes in nanoscale
and time intervals of femtoseconds (International System of Units: fs = 10-
15 = 1 millionth of a billionth of a second ). The technique is to 'fit' in
sequence thousands of 'frames' obtained according to a time scan accurately
defined(85)
.
______________
(84) Source: Italian medicines agency AIFA, Bits from the World, n. 603, Rome
September 9, 2014; Abstract: T. Smith, C. Salgado, PD Mauldin, J. Zhang, JA Bosso /
Medical University of South Carolina, Charleston, South Carolina), Relationship
between days in hospital and infection with resistant pathogenic Gram-negative
Multidrug (study presented in the 54th Interscience Conference on Antimicrobial
Agents and Chemotherapy 2014); Database: Bodies 079-Epidemiology of multi-
resistance, Presentation number K-667, Washington, DC The Sept 5-9,
www.abstractonline.com).
(85) Ahmed Zewail, A new technique allows to film the processes that take place in a
cell or the operation of a nano device, Scientific American, October 2010, n. 506.

19. Raimondo Villano
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Other scenarios could unfold thanks to the recent discovery of a new
protein with key cell receptor-mediated endocytosis (process control what
the cell 'matter' or 'export'), in addition to the four notes denominated
adattine(86)
. Understanding the mechanisms that govern this process can be
essential to intervene with new media on cell permeability(87)
.
Promising is also the discovery of a system of crucial sharing of genetic
material between bacteria and, therefore, of greater spread of antibiotic
resistance: the mechanism of the 'type IV secretion', used to move
substances through the cell wall(88)
.
It tries, also, to set up with the technology of polymeric nanoparticles a
prototype vaccine potential inducer of immunity in the long term and
against many viruses and bacteria that awakens the organism's innate
immunity through the activation of a family of receptors important, the toll-
like (Tlr).
Active in this regard are US researchers at Emory University led by Sudhir
Pai them feed, to produce a yellow fever vaccine that can also be universal
platform for the development of other new vaccines.
With nanoparticles, in effect, re-create the same capacity tested on animal
models in which it is observed powerful immunity that lasts for life,
multiplying the production of specific antibodies against various viruses
and bacteria, influence anthrax.
The vaccine nanotechnology could also represent a turning point for many
other diseases including AIDS(89)
. Since the type IV secretion is capable of
distributing genetic material between bacteria, and in particular the genes
of resistance to antibiotics, the mechanism is responsible for the spread of
antibiotic resistance in hospital settings.
It also plays a vital role during the infectious processes in the secretion of
toxins that cause ulcers, whooping cough or severe pneumonia, such as
Legionnaires' disease.
______________
(86) Discovered by a group of researchers led by Joel Dacks of the University of
Alberta and Margaret Robinson of the University of Cambridge. Ref .: The Science, I
am five 'customs' of the cell, October 12, 2011.
(87) Ref .: Jennifer Hirst, Lael D. Barlow, Gabriel Casey Francisco, Daniela A.
Sahlender, NJ Matthew Seaman, Joel B. Dacks, Margaret S. Robinson, The fifth adapter
protein complex, PLoS Biology, October 11, 2011 .
(88) Mechanism revealed in a study by scientists at the University College of London.
(89) Farma 33, A super-vaccine made with nano particles, February 24, 2011.

20. Superbugs & Superdrugs
72
Interesting could be also the studies on cellular protein p53, the 'guardian of
the genome', also called 'protein hub' for the number of connections that
has risen with other proteins and which are essential for the functioning of
the cell(90)
.
These studies could describe the evolution of large-scale 'network'
biological technology, such as bacterial metabolism, and predict with
remarkable accuracy the likelihood of new connections. The resulting
models provide, therefore, new perspectives are useful in understanding the
preferred connection as a phenomenon emerging networks(91)
.
Scientists could find answers from the study of the mechanisms of survival
of pathogenic bacteria in the passage from the host and vice versa: this
opens up new possibilities for the prevention of the same infections. For
example, it was discovered that a sugar solution in the cell membrane of
the bacterium Escherichia coli growing as quickly as it grows in a
hypotonic solution: shooting microscopic video obtained with an
innovative technique show then, that the process is independent of the
osmotic pressure disproving a theory so far accredited on the growth
dynamics of cell membranes.
Stanford researchers have measured accurately the level of osmotic
pressure sufficient to slow the growth of the membrane of Escherichia coli,
concluding that the cell membrane continues to grow in the sugar solution
with a speed equal to that of the normal solution, but the mass produced in
Excess folds in on itself, a bit 'like the skin of raisins. Once back in the
normal solution, the cells reabsorb water, immediately recovering their
shape more turgid(92)
.
An attempt to strengthen the therapeutic aids available along the way of the
use of silver ions dissolved nell'antibiotico(93)
.
______________
(90) Fragkiskos Papadopoulos and colleagues, University of Cyprus, Popularity versus
similarity in growing networks, Nature, 12 September 2012.
(91) Albert-László Barabási, Center for Complex Network Research at Northeastern
University, Network science: luck or reason, Nature 12 September 2012.
(92) Enrique Rojas, Julie A. Theriot, Kerwyn Casey Huang, Stanford University,
Response of Escherichia coli growth rate to osmotic shock, Proceedings of the National
Academy of Sciences, 27 May 2014 no. 21, 7807-7812.
(93) Experiments in this field are conducted by James Collins, a biomedical engineer at
Boston University, and published in the journal Science Translational Medicine
(Source: Ansa, June 22, 2013).

21. Raimondo Villano
73
It is proved, in fact, that in this way the effectiveness of an antibiotic
increases up to 1,000 times, even against resistant bacteria. The silver acts
both making the permeable wall of the bacteria (making, and then, the
pathogen more accessible to the antibiotic) is inducing the bacteria to
produce large amounts of reactive oxygen compounds (free radicals) which
in high amounts are toxic and kill the bacterium itself.
However, silver may have the drawback of toxic effects on humans, so it is
important to understand what are the limits toxicological dosage for a
possible clinical use or, at least, an alternative must understand in detail the
mechanisms of action for groped to replicating molecules using safer for
humans.
Another line of research focuses on genomic monitoring of resistant
bacteria to study its evolution, with the aim of being able to predict the
rapid changes and so find a strategy to block them.
Scientists have focused, for example, on Streptoccoccus PMEN1,
widespread and extremely resistant to drugs, collecting 240 different
samples from around the world since 1984. We analyzed and compared the
genomes of all bacteria isolated, rebuilding the evolutionary history of the
pathogen, and distinguishing between the two different events of genetic
mutation: type 'vertical' (transmitted from a mother cell to a daughter, in
which individual bases are to be replaced or removed from DNA) and type
'horizontal' (bacteria transmitted between neighbors, in which fragments of
genetic material passed physically from one bacterium to another neighbor,
with possible major changes in large areas of the genome).
It was discovered that most of the mutations occurring in time is of type
'horizontal'.
It also emerged that the transfer of genetic material concerned about three
quarters of the genome, affecting some particular areas of DNA, known as
'hotspots' and, specifically, that the areas most affected by the mutations are
those antigens, originating in immune response. As regards, then, the
development of drug resistance, it was observed that mutations vertical are
the most important and that resistant forms of PMEN1 have already begun
to develop around 1970, so with the start of the spread of the use of
antibiotics.
Other research with biotechnology tools point to the remodeling of
antibodies that target different targets on the membrane of bacteria, a
strategy that could lead to antibiotics achieve highly specific and at the
same time to greatly reduce the risk of developing antibiotic resistance.

22. Superbugs & Superdrugs
74
Experimentation in this direction are carried out by researchers at
MedImmune, a company based in Gaithersburg, Maryland(94)
, who have
developed a hybrid antibody from two monoclonal antibodies, or
antibodies with the ability to bind to a 'target' highly specific, that can be
created by genetic engineering techniques and produced in significant
quantities. In particular, the new antibody was obtained starting from two
distinct monoclonal antibodies directed against Pseudomonas aeruginosa
and has proved to be more effective than the administration of both
monoclonal antibodies originating.
The increasing difficulty finding new effective antibiotic molecules
directed research interest towards monoclonal antibodies, which potentially
offer greater specificity and safety, lack of drug interactions and ability to
leverage complementary mode of action than antibiotics, drastically
reducing the risk of the development of further resistance. However, the
fact that monoclonal antibodies bind to very specific targets (tiny regions of
the bacterial membrane) causes that their effectiveness may sometimes
prove to be marginal. However, assuming that an antibody that
simultaneously has a target two molecules of the bacterial membrane might
produce effects rather than a higher, has been developed a technique that
allows the 'melting' in one antibody to two monoclonal antibodies against
Pseudomonas aeruginosa, one of the bacteria resistant to antibiotics among
the most problematic. The monoclonal anti-PSL hits a polysaccharide of
bacterial membrane (PSL) that allows P. aeruginosa to adhere to host cells
and to create bacterial biofilms, while the anti-PcrV monoclonal antibody
blocks the protein that forms the PcrV 'iniettosomi' of the bacterium, ie the
needle-like structures on its surface which allow the injection of bacterial
toxins into the cells of the host.
The subsequent tests performed before in vitro on mice have shown that the
new bispecific engineered antibody, called BiS4aPa, not only has greater
efficacy of the two antibodies are separate but that a simultaneous
administration of antibiotics potentiates the activity.
______________
(94) Antonio Di Giandomenico, Ashley E. Keller, Cuihua Gao, Godfrey J. Rainey, Paul
Warrener, Mareia M. Camara, Jessica Bonnell, Ryan Fleming, Binyam Bezabeh,
Nazzareno Dimasi, Bret R. Sellman, Jamese Hilliard, Caitlin M . Guenther,
Vivekananda Datta, Wei Zhao, Changshou Gao, Xiang-Qing Yu, JoAnn A. Suzich and
C. Kendall Stover, A multifunctional bispecific antibody protects against Pseudomonas
aeruginosa, Science Translational Medicine, Vol. 6, Issue 262, p. 262ra155, 12
November 2014.

23. Raimondo Villano
75
So, it is fine tuning a formulation of BiS4aPa suitable for human
administration, indicated by the abbreviation MEDI3902, and has initiated
a phase I clinical study to assess its safety.
Other scientists conduct studies on understanding the mechanisms by
which Mycobacterium tuberculosis is able to block the maturation of
phagosomes and survive. This would make new light on the action of
intracellular parasitism of certain microorganisms and would open the door
to new treatments. Researchers at the Pasteur Institute in Seoul and Paris
and Institute of Pharmacology and Structural Biology in Toulouse, for
example, have developed in 2010 a new type of essay with which generated
11,000 mutant strain of M. tuberculosis Beijing, subsequently tested in
search of the genes involved in blocking the maturation of phagosomes.
The M. tuberculosis Beijing strain has been associated with recent
outbreaks of tuberculosis in violent form and resistant to multiple drugs,
which may be useful to identify virulence genes in other pathogens. The
research also revealed the role of new lipid molecules in mycobacterial
intracellular parasitism and what defines a potential new therapeutic target,
important given the emergence of strains that cause tuberculosis resistant to
many anti-tuberculosis drugs. Finally, this assay can be easily adapted to
the screening of new antimicrobials(95)
.
______________
(95) Priscille Brodin, Yannick Poquet, Florence Levillain, Isabelle Peguillet, Gerald
Larrouy-Maumus, Martine Gilleron, Fanny Ewann, Thierry Christophe, Denis
Fenistein, Jichan Jang, Mi-Seon Jang, Sei-Jin Park, Jean Rauzier, Olivier Neyrolles ,
High Content Phenotypic Cell-Based Visual Screen IdentifiesMycobacterium
tuberculosis Acyltrehalose-Containing glycolipids Involved in phagosome Remodeling,
PLOS Journal, DOI: 10.1371 / journal.ppat.1001100, September 9, 2010.

24. Raimondo Villano
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8. Author profile

25. Superbugs & Superdrugs
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26. Raimondo Villano
171
Born in 1960. He lives in Rome and Torre Annunziata. Role:
General Manager Villano International Business Team (from
2012); Chiron CEO Publisher, Honorary Member (2013) and
Associate Professor in History of Health Pharmaceutical
Administration Department of Ruggero II University (Miami,
2014), Trader (since 1976), Trader operating financial
independent of bags and forex (since 1983), Knight SMO Malta
(since 2002), President of Chiron Humanitarian Foundation (since 1985).
Academies: History Art Health-Ministry BC, former papal Tiberina, Melitensi
Studies, Medical Tradition Smithsonian Institution-USA, International Society
History Pharmacy, Acc. History Italian Pharmacy, Soc. Napoletana National
History in. h. Noble College Chemical Pharmaceutical. Over 100 conferences
and chairman in dozens of conferences. He collaborates with important
national and international magazines. You Advisory Board Member for the US
Publisher DPC, which publishes in more than 150 nations. Studies: Classical;
degree and abil .: Pharmacy (1985); courses certificates: Medicinal herbs,
Cosmetic Techniques, Corporate Security, HACCP, History, Social Doctrine of
the Church, theology. Degrees h.c.: Human and Social Sciences (2009); History
and Philosophy (2010); Communication Sciences (2013). Master h.c.: Science
Medical Ethics (2010). He was author, organizer and chairman Safety Course for
managers, obtaining the High Patronage of the Head of State and the UN (2000),
Secretary International Committee Biothecnologies Wabt-Unesco 2008-13,
Diplomatic Adviser AEREC dpt ENVA (from 2011), member of World
Academy Biomedical Technology (Unesco 2007-12), 11 years in the Scientific
Committee of the Health Security IBD (company responsible for the security of
the Courts Naples Appeal Court), Board Beaumont Foundation Onlus research
on cancer with the Prefect of Naples (2011-12), member of European Academy
for Economic and Cultural Relations (2004-15). 32 years partner and owner of
the pharmacy. Partner since 1990, Secretary to 29 years 1990-95 and 2000
Rotary Club President Pompeii-Vesuvius; Comm.ni in Rotary District 2100-
Italy: Professional Ethics, Global Action, Computer; among the many
international roles: archeology Pompeii-Carthage; Committee Prize Magna
Grecia. Napoli president, national Coordinator and founder Federation Young
Chemists; Representative National Trade Union Federative. Assistant
Microbiology Fac. F.cia Na (1985-90, Chair Prof. Lembo-Inst. Sup. Health).
International awards: Diploma of Honor for exceptional services individually
in 5 Vie Action by President Rotary International (Evanston 2001: only 100 /

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year / 1.5 million members); Merit Anti-Crime Task Force-Rotary Italy, Albania,
former Yugoslavia, San Marino (Zurich 2001); Sapientia Mundi-Ethics (Rm
2008); Union Legion of Gold-Work (Rm 2010); Veritas in Charitate-Religion
(2011); Bonifaciano-Culture and Society (2011); Norman-Publishing Gold
Medal (Rm 2014); Norman-Health Galen of Pergamum (Rm 2014). National
Awards: Aesculapius-Health Patronage Ministers Council (Rm 1987); LXVIII
Piccinini-Search (Rm 2006); LXV Stramezzi-Health (Rm 2007); Capitolino-
humanitarian activities (Rm 2010); Tiberino-Culture (Rm 2012); LXXIV
Serono-History (Rm 2012), AEREC-Culture (Rm 2013); Merit Public Health
(DPR 2013), Tiberino-Science (Rm 2014). Author of over 730 publications
health, professional, scientific, historical, religious; more than 50 books (many
translated into English, French, some German, Spanish) with prestigious
publishers as Zanichelli and sponsorship by the Ministry of Cultural Heritage,
Unesco, Rotary, University, etc., present in Italian libraries (including:
Quirinale, National Academy Science, Ministries) and more than 40 countries
(including: National Health Institute-USA, Nationale de France, Congress UK),
in cultural institutes, Universities, Museums; a book made its debut at the
Frankfurt Fair. Catalogues: 2000 Outstanding Intellectuals IBC-Cambridge from
2010; OPAC SBN with over 160 works; from 2010 Sheet Authority Ministry
BAC. Various books are appreciated by authorities, including several times the
Head of State and the Holy Father.
Some books: Global Information Society, 1996; Rotary for Man, 2001;
Managing security in Pharmacy (pres. Dr. Renzulli, already the UN Security
Consultant, 2004); Art and history Pharmacy (pres. Professor Ledermann, Presid.
Em. International Pharmacy History Society, 2 ed., 2006); History and activities
of the SMOM (4th ed., 2007); Pharmaceutical meridians between secular ethics
and Catholic moral (pres. Professor Tarro, Comm. Naz.le Bioethics, 3 ed., 2008);
Thesaurus Pharmacologicus (pres. Presid. Pharmacists Italian Dr. Mandelli
2009); Time sculpted silent eternity. Reflections on diachronic investigation for
memory homo faber (pres. Eminent historian Fra 'von Lobstein and critic Prof.
Carosella, 2 ed., 6 repr., 2010); Pharmaceutical business United Naples (Pres .:
Presid. It Accemia. History Pharmacy Dr. Ravens, 2010); Logos and Theophany
in the digital time (pres. Mons. Trafny, President Dpt Science-Faith Pontifical
Cons. Culture, 2012); Religious aspects and ecclesial dimension SMOM (2013).
Among the more than 40 multimedia: Outline art and history pharmacy (patr.
AISF, 2002); Influenza A / H1N1 (patr. Unesco, 2009).

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“There are remedies worse than the disease”
Publilius Syrus, Sentences

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