List of Contributors xix
Preface xxv
About the Editors xxvii
Part I Current Antibiotics and Their Mechanism of Action 1
1 Resistance to Aminoglycosides: Glycomics and the Link to the Human Gut Microbiome 3
Viviana G. Correia, Benedita A. Pinheiro, Ana Luísa Carvalho, and Angelina S. Palma
1.1 Aminoglycosides as Antimicrobial Drugs 3
1.1.1 The Structure of Aminoglycosides 5
1.1.2 Mechanisms of Action 8
1.2 Mechanisms of Resistance 10
1.2.1 Aminoglycoside-Modifying Enzymes 10
1.2.2 Mutation or Modification of Ribosomal Target Sequences 13
1.2.3 Changes in Uptake and Efflux 14
1.3 Development of New AGAs: The Potential of Glycomics 16
1.3.1 Exploitation of Carbohydrate Chemistry to Study Structure-Activity Relationship of Aminoglycoside Derivatives 17
1.3.2 Aminoglycoside Microarrays to Screen Interactions of Antibiotics with RNAs and Proteins 18
1.4 Influence of the Human Microbiome in Aminoglycoside Resistance 20
1.4.1 The Effect of Antibiotic-Induced Alterations 21
1.4.2 A Reservoir of Antibiotic Resistance 24
1.4.3 Strategies to Modulate the Human Microbiome 25
1.5 Conclusions and Outlook 26
Acknowledgments 27
References 28
2 Mechanisms of Action and of Resistance to Quinolones 39
José L. Martínez
2.1 Introduction 39
2.2 Mechanism of Action of Quinolones 40
2.3 Mutations in the Genes Encoding the Targets of Quinolones 41
2.4 Multidrug Efflux Pumps and Quinolone Resistance 42
2.5 Transferable Quinolone Resistance 43
2.6 Stenotrophomonas maltophilia and Its Uncommon Mechanisms of Resistance to Quinolones 46
Acknowledgments 47
References 47
3 Beta-Lactams 57
Luz Balsalobre, Ana Blanco, and Teresa Alarcón
3.1 Introduction 57
3.2 Chemical Structure 58
3.3 Classification and Spectrum of Activity 59
3.3.1 Penicillins 59
3.3.2 Cephalosporins 61
3.3.3 Monobactams 63
3.3.4 Carbapenems 64
3.3.5 Beta-Lactam Associated with Beta-Lactamase Inhibitors 64
3.4 Mechanism of Action 66
3.5 Activity of Beta-Lactams Against Multiresistant Bacteria 68
3.6 Conclusions 70
References 70
4 Glycopeptide Antibiotics: Mechanism of Action and Recent Developments 73
Paramita Sarkar and Jayanta Haldar
4.1 Introduction 73
4.2 Naturally Occurring Glycopeptide Antibiotics 75
4.3 Mechanism of Action of Glycopeptide Antibiotics 76
4.4 Resistance to Glycopeptides 78
4.5 Second-Generation Glycopeptides 79
4.5.1 Telavancin 79
4.5.2 Dalbavancin 80
4.5.3 Oritavancin 80
4.6 Strategies to Overcome Resistance to Glycopeptides 81
4.6.1 Modifications That Enhance the Binding Affinity to Target Pentapeptide 81
4.6.2 Incorporation of Lipophilicity 85
4.6.3 Incorporation of Lipophilic Cationic Moieties to Impart Membrane Disruption Properties 86
4.6.4 Incorporation of Metal Chelating Moiety to Vancomycin to Impart New Mechanism of Action 88
4.7 Glycopeptides Under Clinical Trials 88
4.8 Glycopeptide Antibiotics: The Challenges 90
References 91
5 Current Macrolide Antibiotics and Their Mechanisms of Action 97
S. Lohsen and D.S. Stephens
5.1 Introduction 97
5.2 Structure of Macrolides 99
5.3 Macrolide Mechanisms of Action 101
5.4 Clinical Use of Macrolides 104
5.5 Next-Generation Macrolides and Future Use 107
References 109
Part II Mechanism of Antibiotic Resistance 119
6 Impact of Key and Secondary Drug Resistance Mutations on Structure and Activity of beta-Lactamases 121
Egorov Alexey, Ulyashova Mariya, and Rubtsova Maya
6.1 Introduction 121
6.2 Struct
