A chemocentric view of the molecular structures of antibiotics, their origins, actions, and major categories of resistanceAntibiotics: 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.

Preface ix-xSection I Challenges for Antibiotics 11 Antibiotics: Initial Concepts and Considerations 42 Major Classes of Antibiotics and Their Modes of Action 16Section II Mechanisms: Antibiotic Action by Bacterial Target Class 333 Assembly of the Peptidoglycan Layer of Bacterial Cell Walls 364 Antibiotics That Block Peptidoglycan Assembly and Integrity 685 Antibiotics That Disrupt Membrane Integrity 1026 Antibiotics That Block Protein Synthesis 1147 Antibiotics That Target DNA and RNA Information Transfer 1488 Antibiotics That Block Biosynthesis of the DNA Building Block Deoxythymidylate 164Section III Mechanisms: Bacterial Resistance to Antibiotics 1779 Bacterial Antibiotic Resistance: Overview 18010 Antibiotic Resistance: Modification or Destruction of the Antibiotic 19811 Antibiotic Resistance via Membrane Efflux Pumps 22012 Resistance via Target Modification 23013 Tuberculosis: A Formidable Challenge for Antibiotic Therapy 252Section IV Mechanisms: Antibiotic Biosynthesis 27314 Antibiotic Biosynthesis: Principles 27615 Biosynthesis of Peptide Antibiotics 28816 Biosynthesis of Polyketide Antibiotics 32017 Biosynthesis of Oligosaccharide, Isoprenoid, and C-P Antibiotic Classes 344Section V Opportunities 36318 Underexploited Pathways and Targets for Antibiotics 36619 Prospects for New Molecules and New Targets 398References 421Index 455