Identification of novel regulatory pathways involved in non-enzymatic resistance to aminoglycosides in Pseudomonas aeruginosa

Identification of novel regulatory pathways involved in non-enzymatic resistance to aminoglycosides in Pseudomonas aeruginosa PDF Author: Arnaud Bolard
Publisher:
ISBN:
Category :
Languages : fr
Pages : 337

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Book Description
Les antibiotiques sont des molécules incontournables dans le traitement des infections bactériennes. L'émergence et la dissémination de la résistance aux antibiotiques chez la pathogène opportuniste Pseudomonas aeruginosa, ont amené l'Organisation Mondiale de la Santé à déclarer indispensable le développement de nouvelles approches thérapeutiques pour lutter contre cette bactérie. Bien que certaines alternatives aient été envisagées, la préservation de l'activité d'antibiotiques majeurs tels que les aminosides et la colistine est primordiale. La caractérisation des mécanismes de résistance à ces médicaments est nécessaire pour la mise au point de nouvelles molécules et mieux prendre en charge les patients. Dans ce contexte, nous montrons que des mutations dans le gène fusA1 (codant le facteur d'élongation EF-G1A) et dans l'opéron pmrAB (système à deux composants PmrAB) entrainent une augmentation de la résistance aux aminosides chez des mutants isolés au laboratoire et des souches issues de patients, atteints ou non, de mucoviscidose. Certaines substitutions d'acide aminé dans EF-G1A accroissent les niveaux de résistance de 2 à 16 fois aux quatre sous-classes d'aminosides. Par ailleurs, des changements d'acide aminé dans le système à deux composants PmrAB activent l'expression des gènes PA4773-PA4774-PA4775, et la production de norspermidine et de spermidine. La synthèse de ces polyamines va de pair avec une baisse de 4 à 16 fois de la sensibilité aux aminosides à noyan 2-désoxystreptamine bisubstitué en 4,6 (gentamicine, amikacine et tobramycine). De plus, il apparaît que la résistance des mutants pmrB à la colistine est en partie dépendante de la pompe d'efflux MexXY(OprM), un système impliqué dans la résistance naturelle, adaptative ou acquise aux aminosides. Enfin, nous montrons que les mutants pmrB surproduisent des alcaloïdes contenant un motif azétidine, par une voie de synthèse non-ribosomale et dépendante du quorum sensing. Ces alcaloïdes diminuent la virulence de P. aeruginosa dans le modèle Galleria mellonella.

Identification of novel regulatory pathways involved in non-enzymatic resistance to aminoglycosides in Pseudomonas aeruginosa

Identification of novel regulatory pathways involved in non-enzymatic resistance to aminoglycosides in Pseudomonas aeruginosa PDF Author: Arnaud Bolard
Publisher:
ISBN:
Category :
Languages : fr
Pages : 337

Get Book Here

Book Description
Les antibiotiques sont des molécules incontournables dans le traitement des infections bactériennes. L'émergence et la dissémination de la résistance aux antibiotiques chez la pathogène opportuniste Pseudomonas aeruginosa, ont amené l'Organisation Mondiale de la Santé à déclarer indispensable le développement de nouvelles approches thérapeutiques pour lutter contre cette bactérie. Bien que certaines alternatives aient été envisagées, la préservation de l'activité d'antibiotiques majeurs tels que les aminosides et la colistine est primordiale. La caractérisation des mécanismes de résistance à ces médicaments est nécessaire pour la mise au point de nouvelles molécules et mieux prendre en charge les patients. Dans ce contexte, nous montrons que des mutations dans le gène fusA1 (codant le facteur d'élongation EF-G1A) et dans l'opéron pmrAB (système à deux composants PmrAB) entrainent une augmentation de la résistance aux aminosides chez des mutants isolés au laboratoire et des souches issues de patients, atteints ou non, de mucoviscidose. Certaines substitutions d'acide aminé dans EF-G1A accroissent les niveaux de résistance de 2 à 16 fois aux quatre sous-classes d'aminosides. Par ailleurs, des changements d'acide aminé dans le système à deux composants PmrAB activent l'expression des gènes PA4773-PA4774-PA4775, et la production de norspermidine et de spermidine. La synthèse de ces polyamines va de pair avec une baisse de 4 à 16 fois de la sensibilité aux aminosides à noyan 2-désoxystreptamine bisubstitué en 4,6 (gentamicine, amikacine et tobramycine). De plus, il apparaît que la résistance des mutants pmrB à la colistine est en partie dépendante de la pompe d'efflux MexXY(OprM), un système impliqué dans la résistance naturelle, adaptative ou acquise aux aminosides. Enfin, nous montrons que les mutants pmrB surproduisent des alcaloïdes contenant un motif azétidine, par une voie de synthèse non-ribosomale et dépendante du quorum sensing. Ces alcaloïdes diminuent la virulence de P. aeruginosa dans le modèle Galleria mellonella.

Antimicrobial Drug Resistance

Antimicrobial Drug Resistance PDF Author: Douglas Mayers
Publisher: Springer Science & Business Media
ISBN: 1603275959
Category : Medical
Languages : en
Pages : 692

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Book Description
This ? rst edition of Antimicrobial Drug Resistance grew out of a desire by the editors and authors to have a comprehensive resource of information on antimicrobial drug resistance that encompassed the current information available for bacteria, fungi, protozoa and viruses. We believe that this information will be of value to clinicians, epidemiologists, microbiologists, virologists, parasitologists, public health authorities, medical students and fellows in training. We have endeavored to provide this information in a style which would be accessible to the broad community of persons who are concerned with the impact of drug resistance in our cl- ics and across the broader global communities. Antimicrobial Drug Resistance is divided into Volume 1 which has sections covering a general overview of drug resistance and mechanisms of drug resistance ? rst for classes of drugs and then by individual microbial agents including bacteria, fungi, protozoa and viruses. Volume 2 addresses clinical, epidemiologic and public health aspects of drug resistance along with an overview of the conduct and interpretation of speci? c drug resistance assays. Together, these two volumes offer a comprehensive source of information on drug resistance issues by the experts in each topic.

Mechanisms of antibiotic resistance

Mechanisms of antibiotic resistance PDF Author: Jun Lin
Publisher: Frontiers Media SA
ISBN: 2889195260
Category : Antibiotics
Languages : en
Pages : 226

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Book Description
Antibiotics represent one of the most successful forms of therapy in medicine. But the efficiency of antibiotics is compromised by the growing number of antibiotic-resistant pathogens. Antibiotic resistance, which is implicated in elevated morbidity and mortality rates as well as in the increased treatment costs, is considered to be one of the major global public health threats (www.who.int/drugresistance/en/) and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public (http://ec.europa.eu/dgs/health_consumer/docs/road-map-amr_en.pdf: http://www.who.int/drugresistance/amr_global_action_plan/en/; http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf). Understanding the mechanisms by which bacteria successfully defend themselves against the antibiotic assault represent the main theme of this eBook published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy. The articles in the eBook update the reader on various aspects and mechanisms of antibiotic resistance. A better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics while minimizing the emergence of antibiotic resistance among pathogens.

Principles and Practice of Pediatric Infectious Diseases

Principles and Practice of Pediatric Infectious Diseases PDF Author: Sarah S. Long
Publisher: Saunders
ISBN: 9780702034688
Category : Medical
Languages : en
Pages : 1618

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Book Description
"In print, online, or on your mobile device, Principles and Practice of Pediatric Infectious Disease provides the comprehensive and actionable coverage you need to understand, diagnose, and manage the ever-changing, high-risk clinical problems caused by infectious diseases in children and adolescents. With new chapters, expanded and updated coverage, and increased worldwide perspectives, this authoritative medical reference offers the latest need-to-know information in an easily-accessible, high-yield format for quick answers and fast, effective intervention!"--Publisher's website.

The Pangenome

The Pangenome PDF Author: Hervé Tettelin
Publisher: Springer Nature
ISBN: 3030382818
Category : Science
Languages : en
Pages : 311

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Book Description
This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of the earliest examples of big data in biology that opened biology to the unbounded. The study of genetic variation observed within a species challenges existing views and has profound consequences for our understanding of the fundamental mechanisms underpinning bacterial biology and evolution. The underlying rationale extends well beyond the initial prokaryotic focus to all kingdoms of life and evolves into similar concepts for metagenomes, phenomes and epigenomes. The book’s respective chapters address a range of topics, from the serendipitous emergence of the pan-genome concept and its impacts on the fields of microbiology, vaccinology and antimicrobial resistance, to the study of microbial communities, bioinformatic applications and mathematical models that tie in with complex systems and economic theory. Given its scope, the book will appeal to a broad readership interested in population dynamics, evolutionary biology and genomics.

Resistance of Pseudomonas Aeruginosa

Resistance of Pseudomonas Aeruginosa PDF Author: Michael Robert Withington Brown
Publisher: John Wiley & Sons
ISBN:
Category : Medical
Languages : en
Pages : 360

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Book Description


Molecular Medical Microbiology

Molecular Medical Microbiology PDF Author: Yi-Wei Tang
Publisher: Academic Press
ISBN: 0123977630
Category : Science
Languages : en
Pages : 2214

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Book Description
The molecular age has brought about dramatic changes in medical microbiology, and great leaps in our understanding of the mechanisms of infectious disease. Molecular Medical Microbiology is the first book to synthesise the many new developments in both molecular and clinical research in a single comprehensive resource. This timely and authoritative three-volume work is an invaluable reference source of medical bacteriology. Comprising more than 100 chapters, organized into 17 major sections, the scope of this impressive work is wide-ranging. Written by experts in the field, chapters include cutting-edge information, and clinical overviews for each major bacterial group, in addition to the latest updates on vaccine development, molecular technology and diagnostic technology. Topics covered include bacterial structure, cell function, and genetics; mechanisms of pathogenesis and prevention; antibacterial agents; and infections ranging from gastrointestinal to urinary tract, centrtal nervous system, respiratory tract, and more. - The first comprehensive and accessible reference on molecular medical microbiology - Full color presentation througout - In-depth discussion of individual pathogenic bacteria in a system-oriented approach - Includes a clinical overview for each major bacterial group - Presents the latest information on vaccine development, molecular technology, and diagnostic technology - More than 100 chapters covering all major groups of bacteria - Written by an international panel of authors who are experts in their respective disciplines

Bacterial Persistence

Bacterial Persistence PDF Author: Jan Michiels
Publisher: Humana
ISBN: 9781493928538
Category : Medical
Languages : en
Pages : 0

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Book Description
This volume presents a comprehensive collection of methods that have been instrumental to the current understanding of bacterial persisters. Chapters in the book cover topics ranging from general methods for measuring persister levels in Escherichia coli cultures, protocols for the determination of the persister subpopulation in Candida albicans, quantitative measurements of Type I and Type II persisters using ScanLag, to in vitro and in vivo models for the study of the intracellular activity of antibiotics. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Bacterial Persistence: Methods and Protocols brings together the most respected researchers in bacterial persistence whose studies will remain vital to understanding this field for many years to come.

Bacterial Resistance to Antibiotics

Bacterial Resistance to Antibiotics PDF Author: Boyan B. Bonev
Publisher: John Wiley & Sons
ISBN: 111994077X
Category : Science
Languages : en
Pages : 288

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Book Description
AN AUTHORITATIVE SURVEY OF CURRENT RESEARCH INTO CLINICALLY USEFUL CONVENTIONAL AND NONCONVENTIONAL ANTIBIOTIC THERAPEUTICS Pharmaceutically-active antibiotics revolutionized the treatment of infectious diseases, leading to decreased mortality and increased life expectancy. However, recent years have seen an alarming rise in the number and frequency of antibiotic-resistant "Superbugs." The Centers for Disease Control and Prevention (CDC) estimates that over two million antibiotic-resistant infections occur in the United States annually, resulting in approximately 23,000 deaths. Despite the danger to public health, a minimal number of new antibiotic drugs are currently in development or in clinical trials by major pharmaceutical companies. To prevent reverting back to the pre-antibiotic era—when diseases caused by parasites or infections were virtually untreatable and frequently resulted in death—new and innovative approaches are needed to combat the increasing resistance of pathogenic bacteria to antibiotics. Bacterial Resistance to Antibiotics – From Molecules to Man examines the current state and future direction of research into developing clinically-useful next-generation novel antibiotics. An internationally-recognized team of experts cover topics including glycopeptide antibiotic resistance, anti-tuberculosis agents, anti-virulence therapies, tetracyclines, the molecular and structural determinants of resistance, and more. Presents a multidisciplinary approach for the optimization of novel antibiotics for maximum potency, minimal toxicity, and appropriated degradability Highlights critical aspects that may relieve the problematic medical situation of antibiotic resistance Includes an overview of the genetic and molecular mechanisms of antibiotic resistance Addresses contemporary issues of global public health and longevity Includes full references, author remarks, and color illustrations, graphs, and charts Bacterial Resistance to Antibiotics – From Molecules to Man is a valuable source of up-to-date information for medical practitioners, researchers, academics, and professionals in public health, pharmaceuticals, microbiology, and related fields.

Antibiotics

Antibiotics PDF Author: Claudio O. Gualerzi
Publisher: John Wiley & Sons
ISBN: 3527659706
Category : Medical
Languages : en
Pages : 549

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Book Description
Most of the antibiotics now in use have been discovered more or less by chance, and their mechanisms of action have only been elucidated after their discovery. To meet the medical need for next-generation antibiotics, a more rational approach to antibiotic development is clearly needed. Opening with a general introduction about antimicrobial drugs, their targets and the problem of antibiotic resistance, this reference systematically covers currently known antibiotic classes, their molecular mechanisms and the targets on which they act. Novel targets such as cell signaling networks, riboswitches and bacterial chaperones are covered here, alongside the latest information on the molecular mechanisms of current blockbuster antibiotics. With its broad overview of current and future antibacterial drug development, this unique reference is essential reading for anyone involved in the development and therapeutic application of novel antibiotics.