Antibiotics: Challenges, Mechanisms, Opportunities

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Christopher Walsh (Harvard Medical School, Boston, USA) Timothy Wencewicz (Washington University in St. Louis)

Antibiotics

Challenges, Mechanisms, Opportunities

Christopher Walsh (Harvard Medical School, Boston, USA), Timothy Wencewicz (Washington University in St. Louis)

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English

American Society for Microbiology
01 February 2016

Pharmacology; Molecular biology; Microbiology (non-medical)

Series: ASM Books

A chemocentric view of the molecular structures of antibiotics, their origins, actions, and major categories of resistance

Antibiotics: Challenges, Mechanisms, Opportunities focuses on antibiotics as small organic molecules, from both natural and synthetic sources. Understanding the chemical scaffold and functional group structures of the major classes of clinically useful antibiotics is critical to understanding how antibiotics interact selectively with bacterial targets.

This textbook details how classes of antibiotics interact with five known robust bacterial targets: cell wall assembly and maintenance, membrane integrity, protein synthesis, DNA and RNA information transfer, and the folate pathway to deoxythymidylate. It also addresses the universe of bacterial resistance, from the concept of the resistome to the three major mechanisms of resistance: antibiotic destruction, antibiotic active efflux, and alteration of antibiotic targets. Antibiotics also covers the biosynthetic machinery for the major classes of natural product antibiotics.

Authors Christopher Walsh and Timothy Wencewicz provide compelling answers to these questions:

What are antibiotics? Where do antibiotics come from? How do antibiotics work? Why do antibiotics stop working? How should our limited inventory of effective antibiotics be addressed?

Antibiotics is a textbook for graduate courses in chemical biology, pharmacology, medicinal chemistry, and microbiology and biochemistry courses. It is also a valuable reference for microbiologists, biological and natural product chemists, pharmacologists, and research and development scientists.

By: Christopher Walsh (Harvard Medical School Boston USA), Timothy Wencewicz (Washington University in St. Louis)
Imprint: American Society for Microbiology
Country of Publication: United States
Edition: 2nd edition
Dimensions: Height: 252mm, Width: 178mm, Spine: 25mm
Weight: 1.021kg
ISBN: 9781555819309
ISBN 10: 1555819303
Series: ASM Books
Pages: 477
Publication Date: 01 February 2016
Audience: College/higher education , Professional and scholarly , Primary , Undergraduate
Format: Hardback
Publisher's Status: Active

Preface ix–x Section I Challenges for Antibiotics 1 1 Antibiotics: Initial Concepts and Considerations 4 2 Major Classes of Antibiotics and Their Modes of Action 16 Section II Mechanisms: Antibiotic Action by Bacterial Target Class 33 3 Assembly of the Peptidoglycan Layer of Bacterial Cell Walls 36 4 Antibiotics That Block Peptidoglycan Assembly and Integrity 68 5 Antibiotics That Disrupt Membrane Integrity 102 6 Antibiotics That Block Protein Synthesis 114 7 Antibiotics That Target DNA and RNA Information Transfer 148 8 Antibiotics That Block Biosynthesis of the DNA Building Block Deoxythymidylate 164 Section III Mechanisms: Bacterial Resistance to Antibiotics 177 9 Bacterial Antibiotic Resistance: Overview 180 10 Antibiotic Resistance: Modification or Destruction of the Antibiotic 198 11 Antibiotic Resistance via Membrane Efflux Pumps 220 12 Resistance via Target Modification 230 13 Tuberculosis: A Formidable Challenge for Antibiotic Therapy 252 Section IV Mechanisms: Antibiotic Biosynthesis 273 14 Antibiotic Biosynthesis: Principles 276 15 Biosynthesis of Peptide Antibiotics 288 16 Biosynthesis of Polyketide Antibiotics 320 17 Biosynthesis of Oligosaccharide, Isoprenoid, and C-P Antibiotic Classes 344 Section V Opportunities 363 18 Underexploited Pathways and Targets for Antibiotics 366 19 Prospects for New Molecules and New Targets 398 References 421 Index 455

Christopher Walsh is a Harvard Medical School professor emeritus who serves as a senior advisor to the ChEM-H Center at Stanford University. He has authored hundreds of papers and books, including the predecessor to this title, Antibiotics: Origins, Actions, Resistance (2003). Dr. Walsh is a member of the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society and a co-recipient of the 2010 Welch Prize in Chemistry. Timothy Wencewicz is a faculty member in the Department of Chemistry at Washington University in St. Louis. After receiving his PhD at the University of Notre Dame, he was a postdoctoral fellow in Christopher Walsh's laboratory at the Harvard Medical School. Dr. Wencewicz's research centers on antibiotic drug discovery, natural product biosynthesis, and targeted drug delivery across bacterial membranes.

Reviews for Antibiotics: Challenges, Mechanisms, Opportunities

-This book provides all the information needed to understand antibiotic genetics, biochemistry, mechanism of action and resistance. Most importantly, Walsh & Wencewicz are optimistic of the prospects of the discovery of novel therapeutic agents obtained by the manipulation of strains and biosynthetic pathways. This beautifully written book deserves to be read and implemented by everyone, especially the pessimists who believe that the antibiotic era has ended. In Antibiotics: Challenges, Mechanisms, Opportunities, Walsh & Wencewicz provide the definitive, ultimate compendium of everything antibiotic.- -- Julian Davies, Professor of Microbiology and Immunology, Life Sciences Institute, University of British Columbia Vancouver