Non-traditional Approaches to Combat Antimicrobial Drug Resistance

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