Non-traditional Approaches to Combat Antimicrobial Drug Resistance

This book provides a detailed overview of the progress and challenges of non-traditional approaches for tackling antimicrobial resistance. The first chapter covers the factors that make microbes more likely to develop multidrug resistance. The book goes on to discuss the antimicrobial properties of propolis, essential oils and other microbial constituents that are used or under investigation to treat multidrug-resistant infections. Additionally, it covers alternative compounds that work as antimicrobial agents, their mechanisms of action, and how they might be utilized in conjunction with conventional drugs to circumvent drug resistance. The book explores the application of phage therapy and recent advancements in phage-based infection control with an emphasis on multidrug-resistant infections and discusses drug repurposing as a strategy to develop new antimicrobial agents efficiently and expeditiously. Additionally, it discusses the uses of nanoparticles in the treatment of infections brought on by multidrug-resistant pathogens and examines the use of different nanotechnology-based approaches to fudge microbial resistance mechanisms. It concludes by reviewing recent studies on microbial quorum-sensing systems and focuses on the significance of quorum-sensing systems in controlling microbial resistance mechanisms and at the same time highlights the importance and role of antimicrobial stewardship program to fight microbial infections. The book is an invaluable source of knowledge and information for academics, basic and clinical researchers, clinicians, and paramedic staff involved in one way or the other in the development and use of antimicrobial agents and strategies to combat multidrug resistance.​

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Table of contents :

Foreword
Preface
Contents
About the Editors
1: Recent Strategies to Combat Multidrug Resistance
1 Introduction and Background
1.1 Multidrug Resistance
1.2 Global Incidences
1.3 Economic Impact
1.4 Currently Available Therapies
1.5 Need for Alternative Therapies
2 Nanotechnology to Combat MDR
3 Quorum Sensing and Biofilms
3.1 QS Network
Cyclic di-GMP (c-di-GMP)
3.2 Biofilm-Associated Antimicrobial Resistance
4 Strategies to Inhibit the Biofilm Formation
4.1 Targeting Initial Stages of Biofilm
4.2 Surface Coating
4.3 Affecting Pili and Flagella
4.4 Inhibiting the Production of EPS
4.5 Reducing Polysaccharide Production
4.6 Reducing Matrix Protein Production
4.7 Reducing eDNA Production
4.8 Inhibiting QS System
4.9 Anti-Virulence Compounds
4.10 Phage Therapy
4.11 Antimicrobial Peptides
5 Conclusion
References
2: The Role of Advanced Therapeutic Techniques to Combat Multi-drug Resistance
1 Introduction
1.1 Non-traditional Approaches to Counter Multi-drug Resistance
Bacteriophage-Based Strategy
Quorum Sensing
Targeted Laser Therapy
CRISPR-Cas
2 Bacteriophage-Based Strategy
2.1 Bacteriophages Can Be Used to Combat Various Multi-drug-Resistant Bacterial Isolates
2.2 Bacteriophages Can Be Used to Combat Multi-drug-Resistant Acinetobacter baumannii
2.3 Bacteriophages Can Be Used to Inhibit Multi-drug-Resistant P. Aeruginosa
2.4 Bacteriophages Can Be Used to Treat Multi-drug-Resistant Salmonella serovars
3 Quorum Sensing
3.1 Application of Quorum Sensing to Inhibit Multi-drug-Resistant P. aeruginosa
3.2 Application of Quorum Sensing to Suppress Multi-drug-Resistant Vibrio cholerae
3.3 Utilisation of Quorum Sensing to Suppress Multi-drug-Resistant E. coli
3.4 Utilisation of Quorum Sensing to Counter Multi-drug-Resistant Chromobacterium violaceum
4 Laser Therapy
4.1 Efficiency of Laser Therapy to Inhibit Different Multi-drug-Resistant Bacterial Pathogens
4.2 Effectiveness of Laser Therapy to Attenuate Multi-drug-Resistant Mycobacterium tuberculosis
5 CRISPR-Cas
5.1 Activity of CRISPR-Cas to Suppress Diverse Multi-drug-Resistant K. pneumoniae
5.2 Activity of CRISPR-Cas to Counter Various Multi-drug-Resistant Osteosarcoma Malignancies
6 Discussion and Conclusion
References
3: Strategies to Combat Multidrug Resistance by Non-traditional Therapeutic Approaches
1 Introduction
2 Antibiotic Failure due to Multidrug Efflux Pumps
3 Anti-virulence
4 Toxins
5 Microbiome-Modifying Therapies
6 Nanomedicine: A Novel Approach
7 Non-traditional Approaches
7.1 Anti-virulence Approaches
Targeting Toxins
Adhesins and Biofilms
Inhibitors of Specialized Bacterial Secretory Systems
VF Secretion
Inhibitors of Organism-Specific Cell-to-Cell Signaling or Bacterial Communication
Counteracting Immune Evasion
8 Microbiome-Modifying Therapies
9 Phage Therapy
9.1 Phages as Carriers
9.2 Phage-Derived Products
10 Immunotherapy
11 Other Bio-antibacterial Approaches
11.1 Antimicrobial Peptides (AMPs)
11.2 Bacteriocins
11.3 Peptide Nucleic Acid (PNA)
11.4 Nanoparticles
11.5 Antisense RNA
11.6 Resistance Modulation and Removal of Drug-Resistant Plasmids
12 Utilizing Emerging Drug Targets in Drug Development
12.1 Targeting Iron Acquisition and Storage
12.2 Targeting Membrane Protein Large
12.3 Targeting ClpP Protease
12.4 Targeting Central Carbon Metabolism
12.5 Targeting Energy Generation Which Further Inhibits Respiratory Chain and ATP Synthesis
12.6 Targeting ROS and NOS
13 Drug Repurposing: Combination Therapies of Multiple-Drug Resistance (MDR)
13.1 Drug Repurposing
14 Difference Between Traditional Drug Discovery and Drug Repurposing
15 Drug Repurposing Strategies
15.1 Drug Repurposing Approaches
16 Mechanisms of Microbial Drug Resistance
17 The Use of Combination Therapy to Counter Multidrug Resistance
18 Future Perspective
References
4: Treatment Strategies to Combat Multidrug Resistance (MDR) in Bacteria
1 Background
2 MDR
3 Global Incidence
4 Economic Impact
5 Currently Available Therapies
5.1 Polymyxins
Mechanism of Action
5.2 Aminoglycosides
5.3 Tigecycline
5.4 Fosfomycin
5.5 Ceftolozane/Tazobactam
5.6 Ceftazidime/Avibactam
5.7 Eravacycline
5.8 Meropenem/Vaborbactam
5.9 Linezolid
5.10 Iclaprim
5.11 Daptomycin
6 Non-traditional Approaches
6.1 Anti-Virulence Factors
6.2 Targeting Biofilms
6.3 Targeting Quorum Sensing
6.4 Drugs Repurposed as Antibiotics
7 Conclusion
References
5: Alternative Therapy Options for Pathogenic Yeasts: Targeting Virulence Factors with Non-conventional Antifungals
1 Introduction
1.1 Global Burden of Yeast Infections and Associated Risk Factors
1.2 Antifungal Resistance and Need for Alternative Therapies
2 Virulence Factors as Alternative Therapeutic Targets in Pathogenic Yeasts
2.1 Virulence Factors: Overview and Therapeutic Concepts
2.2 Inhibition of Biofilm Formation
2.3 Inhibition of Morphogenesis: Yeast-to-Hyphae Transition
2.4 Inhibition of Secreted Aspartic Proteinases
2.5 Inhibition of Prostaglandin E2 Production
2.6 Inhibition of Polysaccharide Capsule and Other Virulence Factors of Cryptococcus Spp.
3 Alternative Therapeutics for Pathogenic Yeasts
3.1 Natural Antifungal Peptides
3.2 Probiotics
3.3 Nanoparticles and Antifungal Drug Delivery
3.4 Phytochemicals and Essential Oils
3.5 Antifungal Free Fatty Acids and Derivatives
3.6 Antifungal Photodynamic Therapy
3.7 Antifungal Vaccines and Immunotherapeutics
4 Conclusions and Future Considerations
References
6: Role of Bacteriophages as Non-traditional Approaches to Combat Multidrug Resistance
1 Introduction
1.1 Multidrug Resistance and Development of Multidrug Resistance
1.2 Classification of Bacteriophages
1.3 Genome Structure of Bacteriophages
2 Culture and Characterization of Bacteriophages
3 Phage Therapy against Multidrug Resistance Pathogens
4 Phage Engineering and Antimicrobial Activity
4.1 Phage Engineering andits Role in Widening the Antimicrobial Spectra
4.2 Phage Engineering and Reduced Host Immune Response
4.3 Phage Engineering and Enhanced Antimicrobial Efficacy
4.4 Bacteriophages and CRISPR-Cas System
5 Phage-Based Proteins as Antibacterial Agents
5.1 Polysaccharide Depolymerases (PSDs)
5.2 Virion-Associated Peptidoglycan Hydrolases (VAPGHs)
5.3 Endolysins
5.4 Holins
5.5 Pyocin
6 Phage-Based Pathogen Detection
6.1 Identification of Bacterial Pathogens Using Antibody-Based Method
6.2 Labelled Phages
6.3 Ice Nuclease Reporter Bacteriophages
6.4 Phage-Based Biosensors
7 Phage-Based Vaccine Development
8 Future Prospects
8.1 Bacteriophages as an Emerging Tool to Control Antimicrobial Resistance
8.2 Bacteriophages and their Role in One Health Approach
8.3 Possibility of Microbial Resistance against Bacteriophages
9 Conclusion
References
7: Drug Repurposing: An Approach for Reducing Multidrug Resistance
1 Background
2 Multidrug Resistance (MDR): The Problem
3 Drug Repurposing: A New Alternative Approach
3.1 Mechanism of Repurposing
Biological Methods
Computational Methods
4 Database Resources for Repurposing
5 Chemical Structure and Molecule Information Strategy
6 Challenges in Drug Repurposing
7 Rationale for Drug Repurposing
8 Advantages of Drug Repurposing
9 Conclusion
References
8: Quorum Sensing as an Alternative Approach to Combatting Multidrug Resistance
1 Introduction
2 Quorum-Sensing Regulation Mechanism
3 Quorum Sensing in Gram-Positive Bacteria
3.1 Streptococcus pneumoniae ComD/ComE Competence System
3.2 Bacillus subtilis ComP/ComA Competence/Sporulation System
Competence
Sporulation
3.3 Staphylococcus aureus AgrC/AgrA Virulence System
4 Quorum Sensing in Gram-Negative Bacteria
4.1 Vibrio fischeri LUXI/LUXR Bioluminescence System
4.2 Pseudomonas aeruginosa LasI/LasR-RhlI/RhIR Virulence System
5 Quorum Sensing in Fungi
6 The Role of Quorum Sensing in Fungal Adaptation Strategies
6.1 QS Regulation of Fungal Morphology
6.2 QS Mechanisms Associated with Inter- and Intraspecies Communication
6.3 Quorum Sensing and Fungal Infections
6.4 QS Molecules and Virulence Factor Modulation
6.5 QS Molecule Control of Cell Shape, Size, or Physiological Status
7 Regulation of the Microbial Resistance by Quorum Sensing and Biofilm Inhibition
8 Biofilms
8.1 Biofilms in Gram-Positive and Gram-Negative Bacteria
The Role of Cell Wall Components in Biofilm Formation
The Role of Motility in Biofilm Formation
The Role of Biofilm Matrix Components in Biofilm Formation
8.2 Biofilms in Fungi
Matrix Composition
Host Immunity and Candida Biofilm Interactions
Aspergillus
Matrix Production
Host Immunity and Aspergillus Interactions
Saccharomyces Cerevisiae
Molecular Basis for Yeast Biofilm Formation
Molecular Basis for Cell Surface Adhesion
Quorum Sensing
Extracellular Matrix and Biofilm Resistance
References
9: Nanoengineering Approaches to Fight Multidrug-Resistant Bacteria
1 Introduction
2 Advantage of Nanotechnology-Based Approach to Fight MDR Bacteria
3 The Mechanisms of Antimicrobial Resistance
4 Classification of Infections
5 Effect of Nanoparticles on the Bacterial Resistance
6 Can Nanoparticles Cause Bacterial Resistance?
7 Designing Nanoparticles as Antimicrobial Agents
7.1 Inorganic and Metallic Nanoparticles
7.2 Antibiotic-Conjugated Nanoparticles
7.3 Small Molecule-Conjugated Nanoparticles
7.4 Antimicrobial Peptide-Conjugated Nanoparticles
7.5 Antimicrobial Peptide-Conjugated Organic Nanoparticles
8 Mechanisms of Antimicrobial Activity of Nanoparticles
9 Conclusions and Prospect
References
10: Quorum Sensing-Mediated Targeted Delivery of Antibiotics
1 Introduction
2 Bacterial Resistance to Antibiotics
3 Bacterial QS Systems
3.1 QS in Gram-Positive Bacteria
3.2 QS in Gram-Negative Bacteria
4 QS Antagonists and Agonists
4.1 Natural Product-Based and Natural Product-Derived QS Inhibitors
4.2 Synthetic QS Inhibitors
5 QS Mediated Delivery: Design
6 Conclusions
References
11: Metal Chelation as a Promising Strategy to Combat Fungal Drug Resistance
1 Introduction
2 Chemistry and Biology of Magnesium
3 Significance of Magnesium in Yeast
4 Magnesium Channels
5 ALR1 and ALR2
6 MRS2
7 MNR2 and LPE10
8 Magnesium Exchange Mechanism
9 Targeting Mg Homeostasis Against Candida
10 Conclusion
References
12: Propolis: A Natural Antibiotic to Combat Multidrug-Resistant Bacteria
1 Introduction
2 Propolis: A Natural Antibiotic
3 Propolis: An Effective Alternative Medicine Against MDR Microbes
4 Synergistic Effects of Propolis with Different Antibiotics Against MDR Microbes
5 Role of Propolis as an Anti-Biofilm and Anti-Quorum Sensing Agent
6 Conclusions
References
13: Therapeutic Potential of Himalayan Ayurvedic Herbs Against Multidrug-Resistant Fungal Pathogens
1 Introduction
2 Fungal Pathogens
3 Current Antifungal Agents and Their Toxicity
4 Himalayan Medicinal Plants and Their Therapeutic Potential
5 Conclusion
References
14: Antimicrobial Stewardship Programme: Why Is It Needed?
1 Introduction
2 Antibiotic Resistance
3 Mechanism of Antibiotic Action
4 Emergence of Antibiotic Resistance
5 Drivers for Resistance
6 Clinical and Economic Consequences of Antibiotic Resistance
7 Stewardship a Key to Combat the Antibiotic Resistance
8 Antibiotic Stewardship Programmes and the COVID-19 Pandemic
References