Antimicrobial Drug Discovery: Emerging Strategies (Advances in Molecular and Cellular Microbiology)

## Abstract This book, inclusive of 22 chapters, describes novel approaches currently used for antimicrobial drug discovery, focusing on agents for use against bacterial and fungal pathogens. Specific chapters discuss: (1) concepts relevant to drug resistance; (2) microbial mechanisms related to efflux pumps and studies on their potential inhibitors; (3) impact of multidrug tolerance of biofilms and persister cells; (4) bacterial quorum-sensing inhibition; (5) inhibition of the bacterial filamentous temperature-sensitive mutant Z (FtsZ); (6) antibacterial properties of lysostaphin; (7) strategies to identify modified ribosomally synthesized antimicrobials; (8) quantitative structure-activity relationship studies of novel antimicrobial peptides; (9) bacterial acetyl-CoA carboxylase and lipopolysacharide as drug targets for antibiotic development; (10) pathosystematic systems biology for the rational design of novel antifungal compounds; (11) specific animal models for novel antimicrobial discovery; and (12) new antimicrobial technology platforms such as antimicrobial photodynamic therapy and carbon nanotubes. Emerging Discovery Strategies : An Evolving Necessity / Anthony R. Ball And George P. Tegos -- The Antibiotic Crisis / Arnold L. Demain And Jaroslav Spizek -- Structure, Genetic Regulation, Physiology And Function Of The Acrab-tolc Efflux Pump Of Escerichia Coli And Salmonella / Leonard Amaral ... [et Al.] -- Small Molecule Efflux Pump Inhibitors From Natural Products As A Potential Source Of Antimicrobial Agents / Sanjay M. Jachak ... [et Al.] -- Fungal Efflux-mediated Resistance : From Targets To Inhibitors / Brian C. Monk ... [et Al.] -- Vacuolar Atpase (v-atpase) : A Model Proton Pump For Antifungal Drug Discovery -- Karlett J Parra -- Drug Tolerance, Persister Cells And Drug Discovery / Kim Lewis -- Inhibition Of Quorum Sensing As A Novel Antimicrobial Strategy -- Gilles Brackman, Hans J. Nelis And Tom Coenye -- Filamentous Temperature-sensitive Mutant Z (ftsz) Protein As An Antibacterial Target / Jaroslaw M. Boberek ... [et Al.] --^ Lysostaphin : A Silver Bullet For Staph / John F. Kokai-kun -- Strategies To Identify Modified Ribosomally Synthesized Antimicrobials -- Alan J. Marsh ... [et Al.] -- Qsar Based Discovery Of Antimicrobial Peptides Active Against Multidrug Resistant Bacteria / Christopher D. Fjell ... [et Al.] -- Acetyl-coa Carboxylase As A Target For Antibacterial Development / Grover L. Waldrop -- Underexploited Targets In Lps Biogenenesis For The Design Of Antibacterials / Laura Cipolla ... [et Al.] -- Predicting And Dissecting Biomolecular Interactions By Information-driven Docking / Panagiotis Kastritsis & Alexandre M.j.j Bonvin -- Anti-fungals And Anti-fungal Drug Discovery / Richard Calderone ... [et Al.] -- Pathosystematic Studies And The Rational Design Of Antifungal Interventions / Elaine M Bignell And Darius Armstrong-james -- In Vivo High-throughput Antimicrobial Discovery Screens Utilizing Caenorhabditis Elegans As An Alternative Host / Jeffrey J. Coleman And Eleftherios Mylonakis --^ Drosophila Melanogaster As A Versatile Model For Discovery Of Drugs Effective Against Human Microbe-induced Infection And Pathology / Yiorgos Apidianakis And Dimitrios P. Kontoyiannis -- Antimicrobial Photosensitizers -- Harnessing The Power Of Light To Treat Infections / Sulbha K Sharma, Tianhong Dai And Michael R Hamblin -- Nanoparticle Platforms For Antimicrobial Therapy / David Trofa, Joshua D. Nosanchuk -- Antimicrobial Activity Of Carbon Nanotubes / Shaobin Liu, Yuan Chen. Edited By George Tegos And Eleftherios Mylonakis. Includes Bibliographical References And Index. Contents......Page 6 Contributors......Page 8 Dedication......Page 12 Introduction......Page 14 1 Emerging Antimicrobial Drug-discovery Strategies: an Evolving Necessity......Page 20 2 The Antibiotic Crisis......Page 39 3 Structure, Genetic Regulation, Physiology and Function of the AcrAB–TolC Efflux Pump of Escherichia coli and Salmonella......Page 57 4 Small-molecule Efflux Pump Inhibitors from Natural Products as a Potential Source of Antimicrobial Agents......Page 75 5 Fungal Efflux-mediated Resistance: from Targets to Inhibitors......Page 90 6 Vacuolar ATPase: a Model Proton Pump for Antifungal Drug Discovery......Page 102 7 Drug Tolerance, Persister Cells and Drug Discovery......Page 114 8 Inhibition of Quorum Sensing as a Novel Antimicrobial Strategy......Page 128 9 Filamentous Temperature-sensitive Mutant Z (FtsZ) Protein as an Antibacterial Target......Page 148 10 Lysostaphin: a Silver Bullet for Staph......Page 160 11 Strategies to Identify Modified Ribosomally Synthesized Antimicrobials......Page 179 12 Quantitative Structure–Activity Relationship-based Discovery of Antimicrobial Peptides Active Against Multidrug-resistant Bacteria......Page 200 13 Acetyl-CoA Carboxylase as a Target for Antibacterial Development......Page 221 14 Underexploited Targets in Lipopolysaccharide Biogenesis for the Design of Antibacterials......Page 233 15 Predicting and Dissecting High-order Molecular Complexity by Information-driven Biomolecular Docking......Page 245 16 Antifungals and Antifungal Drug Discovery......Page 260 17 Pathosystematic Studies and the Rational Design of Antifungal Interventions......Page 278 18 In Vivo High-throughput Antimicrobial Discovery Screens Utilizing Caenorhabditis elegans as an Alternative Host......Page 305 19 Drosophila melanogaster as a Versatile Model for the Discovery of Drugs Effective against Human Microbe-induced Infection and Pathology......Page 313 20 Antimicrobial Photosensitizers: Harnessing the Power of Light to Treat Infections......Page 323 21 Nanoparticle Platforms for Antimicrobial Therapy......Page 336 22 Antimicrobial Activity of Carbon Nanotubes......Page 351 A......Page 362 C......Page 363 E......Page 364 H......Page 365 L......Page 366 N......Page 367 P......Page 368 S......Page 369 Z......Page 370 This book documents the latest research, covering current and promising activities in four key areas: computational chemistry and chemoinformatics, High Throughput Screening (HTS), non-vertebrate model hosts and light and nano-based technologies.