Alternatives to Antibiotics: Recent Trends and Future Prospects

Description

This book discusses prospective alternative approaches to fight bacterial infections to minimize the indiscriminate use of conventional antibiotics. It offers the current knowledge on research and development of alternative antibacterial agents such as probiotics, nanobiotics etc. while it also discusses newly emerging trends such as phage therapy, antibody therapy etc. The book highlights on the phytochemicals with potent antibacterial activities as alternatives to conventional antibiotics. Chemical modification to develop next generation antibiotics with enhanced efficacy has also been included. Such modifications are reported to overcome the inherent resistance of the parent antibiotics. Phage therapy and targeted antibodies are considered as potential alternative approaches to treat bacterial ailments and represent areas of cutting-edge research and have therefore been discussed with sufficient care. Mainly, the book highlights various approaches other than conventional antibiotics in treating bacterial infections. The scientific advancements in these areas will strengthen the ‘One Health’ approach benefiting human beings, animals and environment as well. This book is a comprehensive resource to cater researchers, biological scientists, herbalists and clinical practitioners with up-to-date information on antibacterials other than antibiotics. Foreword Preface Acknowledgement Contents Editors and Contributors Part I: Introductory Chapter Chapter 1: Quest for Alternatives to Antibiotics: An Urgent Need of the Twenty-First Century 1.1 Introduction 1.2 Historical Perspectives of Antibiotic Resistance 1.3 Alternative Strategies to Overcome Antibiotic Resistance 1.3.1 Natural Alternative Approaches 1.3.1.1 Phytochemicals 1.3.1.2 Bacteriophage 1.3.1.3 Antivirulence Therapy 1.3.1.4 Antibodies 1.3.2 Chemical Alternative Approaches 1.3.3 Nanomaterial-Based Alternative Approaches 1.3.4 Probiotics, Prebiotics, Synbiotics and Other Alternative Approaches 1.3.4.1 Probiotics 1.3.4.2 Prebiotics 1.3.4.3 Vaccines 1.3.4.4 CRISPR-Cas9 1.4 Future Prospects 1.5 Conclusion References Part II: Natural Alternative Approaches Chapter 2: Phytochemicals as Antibacterial Agents: Current Status and Future Perspective 2.1 Introduction 2.2 Secondary Metabolites Acting as Antimicrobial Agent 2.2.1 Phenolic Compounds 2.2.2 Quinones 2.2.3 Flavonoids and Their Derivatives 2.2.4 Tannins 2.2.5 Alkaloids 2.2.6 Terpenoids 2.2.7 Sulfur-Containing Phytochemicals 2.3 Quorum Sensing (QS) 2.4 Future Prospects 2.5 Conclusion References Chapter 3: Quorum Quenching Enzymes: A Potent Alternative to Conventional Antibiotics 3.1 Introduction 3.2 Quorum Sensing: The Bacterial Way of Communication 3.2.1 Homoserine Lactones 3.2.2 Autoinducing Peptides (AIPs) 3.2.3 Autoinducer-2 3.3 Inhibition of Quorum Sensing 3.4 Quorum Quenchers Against AHL-Mediated Signalling 3.4.1 Quorum Quenching Activity of Lactonases 3.4.1.1 Metallo-β-Lactamase-Like (MLLs) or AiiA-Like Lactonases 3.4.1.2 Phosphoesterase-Like Lactonases (PLLs) 3.4.1.3 Paraoxonases 3.4.2 Role of Acylases in Quorum Quenching 3.4.3 Role of Oxidoreductases in Quorum Quenching 3.4.4 Quorum Quenching Enzymes Against Other Signalling Molecule 3.5 Advancement of Quorum Quenchers Leads to Higher Effectivity 3.5.1 Nanotechnological Approaches 3.5.2 Protein Engineering Approaches 3.5.2.1 Random Design 3.5.2.2 Rational Design 3.6 Medical Applications of Quorum Quenching Enzymes 3.7 Future Prospects 3.8 Conclusion References Chapter 4: Antibodies as Antibacterial Molecules: The New Era of Antibody-Mediated Immunity 4.1 Introduction 4.2 Structure, Classes, and Functions of Antibodies in Host Immunity 4.3 Functions of Antibodies as Antimicrobial Molecules 4.3.1 Antibodies Functioning Directly as Antibacterial Molecules 4.3.2 Antibodies Functioning Indirectly as Antibacterial Molecules 4.3.3 Antibodies Functioning in a Conjugate 4.3.4 Antibodies Functioning by Neutralizing Toxins 4.4 Challenges and Factors to Consider for the Production of Antibacterial Antibodies 4.4.1 Augmentation of Bacterial Infection by Antibodies 4.4.2 Target Site Accessibility for the Antibodies 4.4.3 Bacterial Defense Mechanisms 4.4.4 Tissue Diffusion of Antibodies after Bacterial Infection 4.5 Future Prospects 4.6 Conclusion References Chapter 5: Phage Therapy: Genomics to Applications and Future Prospects 5.1 Introduction 5.1.1 Ancestry of Bacteriophages 5.1.2 Resurrection of Phage Therapy 5.2 Genomic Diversity in Bacteriophages 5.2.1 Genome Size 5.2.2 Role of Metagenomics in Bacteriophage 5.2.3 Single-Stranded DNA Phages 5.2.4 Double-Stranded DNA Phages 5.2.5 Single-Stranded RNA Phages 5.2.6 Double-Stranded RNA Phages 5.3 Bacteriophages as a Therapeutic Agent 5.3.1 Why Bacteriophage Remedy Is Superior than Antibiotics 5.3.2 Antiphage Mechanism of Bacterial Host 5.3.3 Phages and the Human System 5.3.4 Bacteriophage Interaction with the Immune System 5.3.5 How Does the Immune System Work Against Bacteriophages? 5.3.5.1 Phagocytic Response 5.3.5.2 Cytokine Response Against Phage 5.3.5.3 Antibody Response Against Phages 5.3.6 Bacteriophage Pharmacokinetics 5.3.6.1 Topical or Intranasal Applications 5.3.6.2 Intravenous Application of Therapeutic Phages 5.3.6.3 Oral and Intrarectal Administrations of Therapeutic Phages 5.3.7 Bacteriophage-Derived Lysins 5.3.8 Lysin Structure and Mechanism of Action 5.3.8.1 Gram-Positive Specific Phage Lysin 5.3.8.2 Gram-Negative Specific Phage Lysin 5.3.9 Synergistic Approaches with Lysin 5.3.10 Clinical Approach of Lysin 5.4 Genetic Engineering of Bacteriophages 5.4.1 Homologous Recombination-Based Techniques 5.4.2 Bacteriophage Recombineering of Electroporated DNA (BRED) 5.4.3 CRISPR-Cas System-Based Engineering 5.5 Future Prospects 5.5.1 Vaccines 5.5.2 Clinical Phage Therapy and Phage-Assisted Approaches 5.6 Conclusion References Chapter 6: Alternatives to Antibiotics in Animal Farming 6.1 Introduction 6.2 Status of Application of Antibiotics in Livestock Farming 6.3 Antibiotics and Ecosystems 6.4 Mechanisms of Antibiotic Resistance 6.5 Alternatives to Lessen the Use of Antibiotics in Animal Farming 6.5.1 Probiotics 6.5.2 Prebiotics 6.5.3 Phytochemicals 6.5.4 Feed Enzymes 6.5.5 Metallic Elements 6.5.6 Antimicrobial Peptides 6.5.7 Organic Acids 6.5.8 Bacteriophages 6.5.9 Endolysins 6.5.10 Vaccines 6.5.11 CRISPR/Cas9 6.6 Future Prospects 6.7 Conclusion References Part III: Chemical Alternative Approaches Chapter 7: Metal-Catalyzed Synthesis of β-Lactam Antibiotics 7.1 Introduction 7.2 Development Throughout the Last Few Years 7.2.1 Staudinger Reaction 7.2.2 Kinugasa Reaction 7.2.3 C-H Activation Reaction 7.2.4 C-H Insertion 7.2.5 Aza-Reformatsky Reaction 7.2.6 Other Approaches 7.3 Conclusion References Chapter 8: Upgrading the Antibiotic Arsenal Against Gram-Positive Bacteria: Chemical Modifications of Vancomycin 8.1 Introduction 8.2 Mechanism of Action and Resistance 8.3 Strategies to Overcome Vancomycin Resistance 8.3.1 Modifications that Increase the Binding Efficacy to Target Peptide 8.3.1.1 Synthetic Analogues Involving Modifications to the Core Peptide Backbone 8.3.1.2 Modifications to Impart H-Bonding Affinity 8.3.1.3 Modifications Involving Multivalency 8.3.2 Modifications that Confer Membrane-Interacting Properties 8.3.2.1 Alkylated Vancomycin Derivatives 8.3.2.2 Cationic-Lipophilic Vancomycin Derivatives 8.3.2.3 Peptide-Vancomycin Conjugates 8.3.3 Alternative Strategies of Modification of Vancomycin to Overcome Resistance 8.3.4 Modifications Involving Conjugation of Vancomycin of Other Antibiotics 8.4 Future Prospects 8.5 Conclusions References Chapter 9: Heterocyclic Scaffolds in Novel Synthetic Antibacterial Agents 9.1 Introduction 9.2 Natural to Synthetic 9.3 Heterocyclic Scaffolds as Antimicrobial Agents 9.3.1 The Azirine and Aziridine Scaffolds 9.3.2 The Azetidin-2-One (β-Lactam) Scaffold 9.3.3 The Furan/Pyrrole/Thiophene Scaffolds 9.3.4 The Imidazole and Benzimidazole Scaffold 9.3.5 The Triazole Scaffold 9.3.6 The Pyrazole Scaffold 9.3.7 The Quinoline Scaffold 9.3.8 The Quinazoline Scaffold and the Quinazoline-4-(3H)-Ones 9.4 Future Prospects 9.5 Conclusion References Chapter 10: Antibacterial Metal-Organic Frameworks 10.1 Introduction 10.2 Synthesis of Metal-Organic Frameworks (MOFs) 10.3 Bioactive Silver-Organic Frameworks 10.4 Bioactive Copper-Organic Frameworks 10.5 Bioactive Zinc-Organic Frameworks 10.6 Bioactive MOF Nanocomposites 10.7 MOFs for Antibiotic Delivery 10.8 MOFs for Nitric Oxide Delivery 10.9 Mechanisms of Antibacterial Action 10.10 Future Prospects 10.11 Conclusion References Chapter 11: Cationic Amphiphilic Molecules as Bactericidal Agents 11.1 Introduction 11.1.1 Bacterial Infection and the Need for Antibacterial Drugs 11.1.2 Multidrug-Resistant Bacteria and the Search for New Therapeutic Antibacterial Drugs Based on Cationic Amphiphilic Molec... 11.2 Cationic Amphiphilic Molecules (CAMs) 11.2.1 Natural Cationic Amphiphilic Molecules 11.2.2 Synthetic Cationic Amphiphilic Molecules 11.3 Antibacterial Actions of the CAM Drug Molecules and Mechanism 11.4 Synthetic Cationic Amphiphiles in Combination Therapy 11.5 Challenges and Future Perspectives 11.6 Conclusions References Part IV: Nanomaterial Based Alternative Approaches Chapter 12: Polymeric Nanoparticles and Nanocomposites as Antibacterial Agents 12.1 Introduction 12.2 Shape and Properties of Nanocomposites and Nanomaterials 12.3 Synthesis of Various Nanoparticles and Nanocomposites 12.3.1 Synthesis Approach 12.3.1.1 Top-Down Approach 12.3.1.2 Bottom-Up Approach 12.3.1.2.1 Sol-Gel Method 12.3.1.2.2 Coprecipitation 12.3.1.2.3 The Inert Gas Condensation 12.3.1.2.4 Green Synthesis 12.3.1.2.5 Plasma-Based Synthesis 12.3.1.2.6 Aerosol-Based Synthesis 12.4 Polymeric Nanoparticles as Antibacterial Agents 12.4.1 Micelles 12.4.2 Vesicles 12.4.3 Star Polymeric Nanoparticles 12.4.4 Metallic/Inorganic Polymer Hybrid Nanomaterials 12.5 Various Metallic Nanoparticles Used as the Antibacterial Agents 12.6 Future Prospective and Conclusion References Chapter 13: Metallic Nanoparticles and Their Composites as Alternative Antibacterial Therapeutics 13.1 Introduction 13.2 Metallic Nanoparticles as Antibacterial Agents 13.2.1 Silver Nanoparticles (AgNPs) and Its Nanocomposite 13.2.2 Gold Nanoparticles (AuNPs) and Its Nanocomposite 13.2.3 Copper and Copper Oxide Nanoparticles (CuNPs/CuO NPs/Cu2O NPs) and Its Nanocomposite 13.2.4 Iron Nanoparticles (FeNPs) and Its Nanocomposites 13.2.5 Zinc Oxide Nanoparticles (ZnO NPs) and Its Nanocomposites 13.2.5.1 Generation of ROS 13.2.5.2 Release of the Zn2+ Ion 13.2.5.3 Dysfunction of the Membrane 13.2.5.4 The Internalization of the NPs 13.3 Toxicity of Nanoparticles 13.4 Future Prospects 13.5 Conclusion References Chapter 14: Carbon Nanoparticles as the Next-Generation Antimicrobial Agents 14.1 Introduction 14.2 Carbon Nanotubes and Their Antimicrobial Properties 14.2.1 Carbon Nanotubes Damage Bacterial Cell Membranes by Direct Contact 14.2.2 Antimicrobial Activity Is Dependent on CNT Concentration, Buffer, and Treatment Time 14.2.3 The Size of Nanotubes Determines Antimicrobial Activity 14.2.4 Carbon Nanotube Composites and Their Antimicrobial Properties 14.2.5 Carbon Nanotubes for Delivery of Antibiotics 14.3 Fullerenes and Their Antimicrobial Properties 14.3.1 Functionalized Fullerenes Affect Viral Proteases and Possess Bacteriostatic Properties 14.3.2 Fullerenes Affect Microbial Energy Metabolism 14.3.2.1 Lipophilic Nature of Fullerenes Allow for Membrane Permeability 14.3.2.2 Cationic Fullerenes Use ROS-Mediated Antimicrobial Mechanism 14.3.3 Fullerenes Used for Photodynamic Therapy Against Infections 14.3.4 Fullerene Nanocomposites as Antimicrobial Agents 14.4 Antimicrobial Properties Graphene, Graphene Oxide (GO), and Their Derivatives 14.4.1 Graphene and Derivatives Cause Physical Damage to Microbial Membrane 14.4.2 GOs Cause Oxidative Damage to Microbial Cells 14.4.3 Size and Solubility of GO Determines Antimicrobial Activity 14.4.4 GO Nanocomposites in Antimicrobial Therapy 14.4.4.1 Metal Nanocomposites Most Effective Antimicrobial Agents 14.4.4.2 Other GO Nanocomposites and Their Antimicrobial Properties 14.5 Carbon Dots as Emerging Class of Photosensitizers for Antimicrobial Therapy 14.6 Future Perspectives for the Use of Carbon Nanomaterials as Antibiotics: Advantages and Challenges References Chapter 15: Dendrimeric Entities as Chemical Alternatives Toward Antimicrobial Therapy 15.1 Introduction 15.2 Dendrimers: A Brief Introduction 15.3 Why Are Dendrimers Chosen as Antimicrobial Agents? 15.4 Various Classes of Antimicrobial Dendrimers 15.4.1 Glycodendrimers 15.4.2 Cationic Dendrimers 15.4.3 Anionic Dendrimers 15.4.4 Peptide-Based Dendrimers 15.4.5 Organometallic Dendrimers 15.5 Future Prospects 15.6 Conclusion References Chapter 16: Ionic Liquids, Ionic Liquid Nanoparticles, and Nanocomposites: The Future Antibiotics 16.1 Introduction 16.2 Antimicrobial Activity of Ionic Liquids 16.2.1 Antimicrobial Activity of Quaternary Ammonium ILs 16.2.2 Imidazolium Ionic Liquids 16.2.3 Antimicrobial Activity of Pyridinium Ionic Liquids 16.2.4 Antibacterial Activity of Phosphonium Ionic Liquids 16.2.5 Antibacterial Activity of Few Other Ionic Liquids 16.2.6 Antibacterial Activity of Ampicillin and Amoxicillin Ionic Liquids 16.2.7 Antibacterial Activities of Poly Ionic Liquids 16.2.8 Antibacterial Activity of Ionic Liquid Composites and Nanocomposites 16.2.9 Biofilm Resistance of ILs and IL Nanocomposites 16.3 Mechanism of Action 16.4 Future Prospect 16.5 Conclusion References Part V: Probiotics and Other Alternative Approaches Chapter 17: Prebiotic Immunomodulators to Enhance Mucosal Immunity and to Reduce Mass Use of Antibiotics 17.1 Introduction 17.2 Immunity and Its Types 17.2.1 Mucosal Immunity and Its Function in Adaptive Immune Response 17.2.2 Mucosal Immunity in the Gastrointestinal Tract (GIT) 17.2.3 Mucosal Immunity in the Respiratory Tract 17.3 Strategies for Vaccination Harnessing the Aspects of Mucosal Immunity 17.4 Immunomodulators 17.5 Types of Prebiotics 17.6 Prebiotics as Potent Immunomodulatory Agents 17.7 Fructan: A Promising Prebiotic 17.8 Adverse Consequences of Synthetic Immunomodulators 17.9 Adverse Consequences of Antibiotics 17.10 Prebiotics as Promising Alternatives to Antibiotics 17.11 Effects of Prebiotics and Probiotics in Pulmonary Health: In the Context of Current COVID-19 Pandemic 17.12 Future Prospect 17.13 Conclusion References Chapter 18: The Use of Probiotics, Prebiotics, and Synbiotics as an Alternative to Antibiotics 18.1 Introduction 18.2 Probiotics 18.3 Methods to Determine Probiotics as an Antimicrobial Against Another Organism 18.3.1 In Vitro Methods 18.3.2 In Vivo Methods 18.4 Mechanisms of Action in Probiotics 18.4.1 Competitive Inhibition 18.4.2 Production of Antimicrobial Compounds 18.4.3 Immunomodulation 18.5 Probiotics Classified to Be Used as Antimicrobial Agents 18.6 Prebiotics 18.7 Mechanism of Action of Prebiotics 18.7.1 Bifidogenic Effect 18.7.2 Colonization Inhibition 18.7.3 Healthy Gut Maintenance 18.7.4 Immunomodulatory Effects 18.8 Prebiotics Classified to Be Used as Antimicrobial Agents 18.9 Synbiotics 18.10 Mechanism of Action of Synbiotics 18.11 Synbiotics Classified to Be Used in Hosts 18.12 Present Status of the Clinical Status of Probiotics, Prebiotics, and Synbiotics 18.13 Future Prospects 18.14 Conclusion References Chapter 19: The Implication of Antimicrobial Peptides Against Bacteria and Their Clinical Aspects 19.1 Introduction 19.2 Classification of Antimicrobial Peptides 19.2.1 Classification of AMPs Based on Biosynthetic Machines 19.2.2 Based on Biological Sources 19.2.3 Insect´s Antimicrobial Peptides 19.2.4 Antimicrobial Peptides from Microorganisms 19.2.5 Antimicrobial Peptides of Mammals 19.3 Generalized Mechanism of Action of AMPs 19.3.1 Transmembrane Pore Models 19.3.2 Barrel-Stave Pore Model 19.3.3 Toroidal Pore Model 19.3.4 Carpet Model 19.3.5 Molecular Electroporation 19.3.6 Sinking Raft Model 19.4 Categorization of AMPs Based on Their Properties 19.4.1 Categorization of AMPs on Basis of 3D Structure 19.5 Categorization of AMPs Based on Molecular Targets 19.5.1 AMPs Acting on the Synthesis of the Cell Wall of Bacteria 19.5.2 Interaction with Bacterial Membrane 19.5.3 Inhibition of Nucleic Acid Biosynthesis 19.5.4 AMPs Acting on Protein Synthesis 19.6 Clinical Applications 19.7 Future Perspective 19.8 Conclusion References Chapter 20: Development of Probiotics for Helicobacter pylori Infection Management 20.1 Introduction 20.2 Mechanism of Infection by Helicobacter pylori 20.2.1 Entry into Mucosal Layer 20.2.2 Adhesion to Gastric Epithelial Cells 20.2.3 Virulence and Cell Damage 20.2.4 Persistence and Immune Modulation 20.3 Selection and Screening of Suitable Probiotics 20.3.1 Single/Double or Mixed Strain Probiotics Against Helicobacter pylori 20.4 Development of Probiotics for Helicobacter pylori Infection Management 20.4.1 Combinatorial Therapy: Probiotics with Antibiotics 20.4.1.1 Antibiotic Regimens Used for Helicobacter pylori Eradication 20.5 Antibiotic Resistance 20.6 How Can Probiotics Be of Aid? 20.7 Efficacy and Safety of Probiotics for H. pylori Eradication 20.7.1 Efficacy 20.7.2 Safety 20.8 Probiotics for H. pylori: Future Scope and Directions for Research 20.8.1 Shortcomings of Current Infection Management 20.8.2 Strategies to Overcome These Hurdles 20.8.3 Immunity Against H. pylori Infection 20.8.3.1 Vaccines 20.8.3.2 Probiotics for Prevention H. pylori Infection 20.9 Constraints or Risks Associated with Clinical Use of Probiotics 20.10 Regulatory Guidelines Regarding Safety and Efficacy 20.11 Future Prospects 20.12 Summary and Conclusion References Chapter 21: Implications of Probiotics in Management of Bacterial Infections 21.1 Introduction 21.2 Production of Organic Acids and Other Inhibitory Substances 21.3 Bacteriocins 21.4 Competitive Exclusion 21.5 Future Prospects 21.6 Conclusion References Chapter 22: Nanocarriers for the Molecular Targeting of Pathogenic Bacteria 22.1 Antibiotic-Resistant Pathogens 22.2 Advantages of Nanosystems Used for Antibiotic Delivery Vis-à-vis Conventional Antibiotic Therapy 22.3 Lipid Nanocarriers 22.4 Stimuli-Triggered Drug Delivery Systems 22.5 Biocompatible Micelles 22.6 Antimicrobial Peptide Loaded Nano-Composites 22.7 Chitosan-/Alginate-Based Nanomaterials as Antimicrobial Carrier 22.8 Quantum Dots 22.8.1 Cadmium Tellurium Quantum Dots (CdTe QDs) 22.8.2 Graphene Quantum Dots (GQDs) 22.8.3 Zinc Oxide Quantum Dots (ZnO QDs) 22.9 Hydrogen Dendrimers 22.10 Current Limitations and Future Prospects 22.11 Conclusion References Index