Antimicrobial Resistance: Underlying Mechanisms and Therapeutic Approaches

Preface
Contents
About the Editors
1: Antimicrobial Resistance Traits and Resistance Mechanisms in Bacterial Pathogens
1.1 Introduction
1.2 Antibiotics for the Treatment of Infections Caused by ESKAPE Pathogens
1.3 Origin and Evolution of Antimicrobial Resistance Traits in ESKAPE Pathogens.
1.4 Genomic Insights into Antimicrobial-Resistant ESKAPE Pathogens
1.4.1 Gram-Positive ESKAPE (GP-ESKAPE) Pathogens
1.4.1.1 Vancomycin-Resistant Enterococcus
1.4.1.2 Staphylococcus aureus
1.4.2 Gram-Negative ESKAPE (GN-ESKAPE) Pathogens
1.4.2.1 Klebsiella pneumoniae
1.4.2.2 Acinetobacter baumannii
1.4.2.3 Pseudomonas aeruginosa
1.4.2.4 Enterobacter Species
1.5 Ecology of Antimicrobial Resistance Genes in ESKAPE Pathogens
1.5.1 Plasmids
1.5.2 Bacteriophages
1.5.3 Transposons
1.5.4 Integrative and Conjugative Elements (ICEs)
1.5.5 Integrons
1.6 Resistance Mechanisms of ESKAPE Pathogens
1.6.1 Resistance Due to Decreased Permeability or Active Ejection of Antibiotics
1.6.2 Resistance Due to Inactivation of the Antibiotics
1.6.2.1 Inactivation of Antibiotics by Hydrolysis.
1.6.2.2 Inactivation of Antibiotics by Chemical Modifications.
1.6.3 Resistance due to Alteration of the Target Site of the Antibiotic
1.6.3.1 Mutations of the Target Site
1.6.3.2 Enzymatic Modification of the Target Site
1.6.3.3 Target Protection
1.6.3.4 Substitution or Bypassing of the Target Site
1.7 Conclusion
References
2: Bacterial Multidrug Tolerance and Persisters: Understanding the Mechanisms, Clinical Implications, and Treatment Strategies
2.1 Introduction: Bacterial Multidrug Tolerance and Persister Formation
2.2 Similarity and Difference Between Persisters and Resistant Mutants
Box 2.1
2.3 Different Mechanisms of Persister Formation
2.3.1 Nonspecific Determinants
2.3.2 Specific Determinants
2.4 Regrowth of Persisters
2.5 Persisters as Predecessors of Resistant Mutants
2.6 Different Techniques to Study Bacterial Persisters
2.6.1 Time-Kill Curves
2.6.2 Single-Cell-Level Studies
2.6.3 Population-Level Studies.
2.6.4 In Vivo Models and their Relevance
2.6.5 Future Perspectives of in Vivo Techniques
2.7 Persister Formation in Gram-Negative Bacteria
2.8 Persister Formation in Gram-Positive Bacteria
2.9 Persister Formation in Mycobacteria
2.10 Anti-Persister Strategies
2.10.1 Inhibiting Formation of Persisters
2.10.2 Direct Killing of Persister Cells
2.10.2.1 Target Independent
2.10.2.2 Target Dependent
2.10.2.3 Repurposing of Drugs.
2.10.2.4 Novel Approaches
2.11 Conclusion and Perspectives
References
3: Microbial Pathogenesis: Mechanism and Recent Updates on Microbial Diversity of Pathogens
3.1 Diversity of Microorganisms
3.2 Bacteria
3.2.1 Bacterial Pathogenesis
3.2.2 Diseases Caused by Pathogenic Bacteria in Humans
3.2.2.1 Enterococcus faecalis
3.2.2.2 Enterococcus faecium
3.2.2.3 Escherichia coli
3.2.2.4 Pseudomonas aeruginosa
3.2.2.5 Staphylococcus aureus
3.2.2.6 Clostridioides difficile
3.2.2.7 Streptococcus pneumoniae
3.2.2.8 Acinetobacter baumannii
3.2.2.9 Klebsiella pneumoniae
3.2.2.10 Neisseria gonorrhoeae
3.2.2.11 Mycobacterium tuberculosis
3.2.2.12 Helicobacter pylori
3.2.2.13 Campylobacter spp.
3.2.2.14 Salmonella
3.2.2.15 Haemophilus influenzae
3.2.2.16 Shigella spp.
3.3 Archaea
3.3.1 Classification of Archaea
3.3.2 Pathogenicity in Archaea
3.3.3 Pathogenic Archaea
3.4 Fungi
3.4.1 Fungal Classification
3.4.2 Mechanism of Fungal Pathogenesis
3.4.3 Diseases Caused by Pathogenic Fungi in Humans
3.4.3.1 Adiaspiromycosis
3.4.3.2 Aspergillosis
3.4.3.3 Candidiasis
3.4.3.4 Entomophthoromycosis
3.4.3.5 Fungal Keratitis
3.4.3.6 Lobomycosis
3.4.3.7 Pneumocystis Pneumonia
3.4.3.8 Pythiosis
3.4.3.9 Tinea Capitis
3.5 Protozoa
3.5.1 Various Classes of Protozoa
3.5.2 Pathogenesis of Protozoa
3.5.3 Current Scenario of Pathogenic Protozoa
3.5.3.1 Cryptosporidium Species
3.5.3.2 Giardia intestinalis
3.5.3.3 Entamoeba Species
3.5.3.4 Balantidium coli
3.6 Algae
3.6.1 Algal Classification
3.6.2 Microscopic Algae as Pathogens: Mechanism of Pathogenicity
3.6.3 Disease-Causing Algae
3.7 Virus
3.7.1 Classification of Virus
3.7.2 Mechanism of Pathogenesis of Viruses
3.7.3 Deadliest Diseases Caused by Various Strains of Virus in Humans
References
4: Pseudomonas aeruginosa: Pathogenic Adapter Bacteria
4.1 Introduction
4.2 Disease: An Introduction
4.3 P. aeruginosa.
4.3.1 History
4.3.2 Classification
4.3.3 Morphology
4.4 Identification of P. aeruginosa
4.4.1 Biochemical Test and Molecular Identification
4.4.2 Genetics and Molecular Biology
4.5 Pathogenicity, Morbidity, and Mortality of P. aeruginosa
4.6 Prevention
4.7 Treatment Option
4.7.1 Antibiotic Option
4.7.2 Combination Coverage
4.8 Drug Resistance
4.8.1 Porins
4.8.2 Efflux
4.8.3 Biofilm
4.8.4 Metallo-β-Lactamases
4.8.5 Quorum Sensing
4.9 Summary
References
5: Impact of Antibiotic Resistance of Bacteria in Biofilms and Microbial Fuel Cell: Confronting the Dark Box for Global Health...
5.1 Introduction
5.1.1 Antibiotic Resistance
5.1.2 Antibiotics as an Organic Pollutant in Wastewater
5.1.3 Biofilm and Antibiotics
5.2 Molecular Mechanism of Antibiotic Resistance
5.3 Biofilm Resistance and Tolerance
5.4 Bio-Electrochemical Concepts in Wastewater (Microbial Fuel Cell)
5.5 Potential for New Therapies
5.6 Antibiotic Removal Mechanisms Based on Microbial Fuel Cell
5.7 Overall Performance/Discussion of Antibiotic Resistance in Biofilm and Fuel Cells
5.8 Conclusions
References
6: Plant Secondary Metabolites for Tackling Antimicrobial Resistance: A Pharmacological Perspective
6.1 Introduction
6.2 Groups of Antimicrobial Plant Secondary Metabolite
6.2.1 Phenolics
6.2.2 Alkaloids
6.2.3 Saponins
6.2.4 Terpenes
6.2.5 Flavonoids
6.3 Mechanisms/Mode of Action of Plant Secondary Metabolites
6.3.1 Disruption of Plasma Membrane
6.3.2 Inhibition of DNA Replication
6.3.3 Interference of Quorum Sensing
6.3.4 Inhibition of Protein Synthesis
6.3.5 Combinatorial Effect
6.4 Mechanisms of Antimicrobial Resistance
6.5 Pharmacological Significance of Plant Secondary Metabolites in Medicine
6.6 Future Perspectives and Concluding Remarks
References
7: Can Nanoparticles Help in the Battle against Drug-Resistant Bacterial Infections in ``Post-Antibiotic Era´´?
7.1 Introduction
7.2 Antibacterial Activity of Nanoparticles
7.3 In Biofilm Prevention and Disruption
7.4 Quorum Sensing Inhibitors
7.5 Role on Efflux Pumps
7.6 Action on Plasmids
7.7 As delivery Systems to Combat Infections
7.8 Nanoparticles in Detection and Diagnosis of Infection
7.9 Other Contributions of Nanoparticles to Mitigate Drug Resistance
7.10 Have Bacteria Developed Resistance to Nanoparticles?
7.11 Every Rose Has Its Thorn: NPs Worsen AMR Condition
7.12 Conclusion
References
8: Precise Sequence-Specific Antimicrobials Based on CRISPR: Toward Prevailing Over Bacterial Antibiotic Resistance
8.1 Introduction
8.2 Problem(s) Associated with Conventional Antibiotics
8.3 CRISPR/Cas Potential to Serve as Programmable Sequence-Specific Antimicrobials
8.4 Benefits and Advantages of CRISPR-Based Antimicrobials
8.5 Different Types of Available Nucleases for CRISPR Antimicrobials
8.6 CRISPR Antimicrobial Delivery Systems for Targeted Killing or Antibiotic Sensitivity
8.7 Existing Challenges for Sufficient Antimicrobial Activity and Ways of Efficacy Enhancement
8.7.1 Resistance Against CRISPR/Cas Antimicrobials
8.7.2 CRISPR/Cas Common Delivery Vehicles and Associated Challenges
8.7.3 Social Issues of Using CRISPR Antimicrobials
8.8 In Vivo Application of CRISPR Antimicrobials
8.9 Future Prospects
References
9: Antibiotic-Resistant Klebsiella pneumoniae and Targeted Therapy
9.1 Introduction
9.2 Drug Resistance in K. pneumoniae
9.3 Mechanisms of Drug Resistance
9.3.1 Drug Resistance Due to Efflux Pumps
9.3.2 Drug Resistance Due to Porin Loss
9.3.3 Drug Resistance Due to Target Modification
9.3.4 Drug Resistance Due to Alteration of the Drug
9.3.5 Drug Resistance Due to Biofilm Formation
9.4 Novel Therapies to Overcome Drug Resistance in K. pneumoniae Infections
9.4.1 Phage Therapy
9.4.2 Nanoantibiotics
9.4.3 Phytotherapy
9.4.4 Combination Therapy
9.4.5 Antimicrobial Peptides
9.4.6 Photodynamic Therapy
9.5 Conclusion
References
10: Plant-Associated Endophytic Fungi and Its Secondary Metabolites Against Drug-Resistant Pathogenic Microbes
10.1 Introduction
10.1.1 Factors Causing the Resistance in Pathogenic Microbes
10.1.2 Mechanism of Antibiotic Resistance
10.1.3 Endophytes as a Source of Therapeutic Compounds
10.2 Fungal Endophytes Against MRSA
10.2.1 Mechanism of Resistance in S. aureus
10.3 Fungal Endophytes Against Drug-Resistant Plasmodium Sp.
10.4 Fungal Endophytes Against Resistant Mycobacterium Sp.
10.5 Fungal Endophytes Against Resistant Candida albicans
10.6 Miscellaneous
10.7 Discussion and Conclusion
References
11: Antimicrobial Peptides as Effective Agents Against Drug-Resistant Pathogens
11.1 Introduction
11.1.1 Natural Products as Prospective Source to Counter Antimicrobial Resistance
11.1.2 Antimicrobial Drugs: History and Developments
11.2 Antimicrobial Peptides: The Peptide-Based Drugs as Novel Class of Therapeutics to Tackle Antibiotic Resistance
11.2.1 Identification and Properties
11.2.2 Classification and Structure of AMPs
11.2.3 Antimicrobial Peptides and Their Mechanism of Action
11.2.4 AMPs in Clinical Trials as Antimicrobial Therapeutics
11.3 Recent Progress in the Development of Peptide-Based Drugs
11.3.1 Plant-Based Expression System for the Production of AMPs
11.3.1.1 Plant Tissue Culture-Based Expression Systems
11.3.1.2 Genetically Engineered Plant Systems
11.3.1.3 Strategies for Transient Expression
11.3.1.4 Cell Pack Method
11.4 Computational Biology-Based Antimicrobial Research
11.5 Challenges Associated with Development of AMPs as Antimicrobial Therapeutics
11.6 Commercial Success and Prospects of AMPs as Antimicrobial Therapeutics
References
12: Essential Oils for Combating Antimicrobial Resistance: Mechanism Insights and Clinical Uses
12.1 Introduction
12.2 Antibacterial Effects of Essential Oils
12.3 Antibacterial Mechanisms of EOs and Their Bioactive Compounds Against Bacteria
12.3.1 Antibacterial Mechanisms of EOs
12.3.2 Antibacterial Mechanisms of Volatile Bioactive Compounds
12.4 Clinical Investigation of Bioactive Compounds from Essential Oils Against Bacteria
12.5 Conclusions and Perspectives
References
13: Antimicrobial Resistance and Medicinal Plant Products as Potential Alternatives to Antibiotics in Animal Husbandry
13.1 Introduction
13.2 Antibiotic Use in Animal Husbandry
13.3 Antimicrobial Resistance in Animal Husbandry
13.4 Medicinal Plant Resources as Classes of Alternatives
13.4.1 Probiotics
13.4.2 Prebiotics
13.4.3 Synbiotics
13.4.4 Enzymes
13.4.5 Phytogenics
13.4.6 Essential Oils
13.4.7 Phytochemicals
13.4.8 Antimicrobial Peptides
13.5 Medicinal Plant Products Targeting Pathogenicity
13.5.1 Quorum Sensing Inhibitors
13.5.2 Efflux Pump Inhibitors
13.5.3 Bacterial Virulence Inhibitor
13.5.4 Biofilm Inhibitors
References
14: Recent Updates on Bacterial Secondary Metabolites to Overcome Antibiotic Resistance in Gram-Negative Superbugs: Encouragem...
14.1 Introduction
14.1.1 Antibiotic Resistance: A Perfect Storm
14.1.2 Socioeconomic Impact of Antibiotic Resistance
14.2 The Need for New Antibiotics
14.2.1 The Golden Era of Antibiotics Versus the ``Void´´ in the Discovery Pipeline
14.3 Can We Rely Upon Bacterial Hidden Treasure to Find New Antibiotics?
14.3.1 Natural Products Versus Synthetic Compounds
14.3.2 Untapped Bacterial Diversity as a Source of New and Effective Antibiotics
14.3.2.1 Novel Tetracyclines
14.3.2.2 Cefiderocol
14.3.2.3 Bacteriocins
Enterocin E 760
14.3.2.4 Bacteriocin E 50-52 and B 602
14.3.2.5 Macrolactin S
14.3.2.6 Pulvomycin
14.3.2.7 Plazomicin
14.3.2.8 Novel Polymyxin Derivatives
14.3.2.9 Octapeptins
14.3.2.10 Paenibacterin
14.3.2.11 Cystobactamids
14.3.2.12 Paenipeptins
14.3.2.13 Brevicidine and Laterocidin
14.3.2.14 Odilorhabdins
14.3.2.15 Optimized Arylomycins
14.3.2.16 Tridecaptins
14.3.2.17 Darobactin
14.3.2.18 Picolinamycin
14.4 Bacteria as a Potential Source of Antibiotic Adjuvants/Resistance-Modifying Agents (RMAs)
14.4.1 beta-Lactamase Inhibitors (BLI)
14.4.2 Efflux Pump Inhibitors (EPIs)
14.4.3 Quorum Sensing Inhibitors (QSIs)
14.4.4 Biofilm Inhibitors
14.4.5 Outer Membrane Permeabilizers
14.5 Concluding Remarks
References
15: Plant Essential Oils for Combating Antimicrobial Resistance via Re-potentiating the Fading Antibiotic Arsenal
15.1 Introduction
15.2 Methodology
15.3 Possible Mechanism of Action of Essential Oil from Plants in Drug-Resistant Microbes
15.3.1 Mode of Action of Essential Oils in Bacteria
15.3.1.1 Altered Membrane Permeability of Bacterial Cell
15.3.1.2 Bacterial Efflux Pump Inhibition
15.3.1.3 Essential Oil as a Beta-Lactamase Inhibitor
15.3.1.4 Anti-quorum Sensing
15.3.2 Mode of Action of Essential Oils in Fungus
15.3.2.1 Cell Membrane Disruption, Alteration, and Inhibition of Cell Wall Formation
15.3.2.2 Dysfunction of the Fungal Mitochondria
15.3.2.3 Inhibition of Efflux Pump in Fungal Cell Membrane
15.3.3 Mode of Action of Essential Oils in Protozoa
15.3.4 Mode of Action of Essential Oils in Viruses
15.4 Plant-Based Essential Oil Chemistry and Family-Wise Description of In Vitro Antimicrobial Activity of Essential Oil Again...
15.4.1 Annonaceae
15.4.2 Apiaceae
15.4.3 Aristolochiaceae
15.4.4 Asteraceae
15.4.5 Brassicaceae
15.4.6 Lauraceae
15.4.7 Lamiaceae
15.4.8 Moraceae
15.4.9 Myrtaceae
15.4.10 Oleaceae
15.4.11 Poaceae
15.4.12 Rutaceae
15.4.13 Santalaceae
15.4.14 Schisandraceae
15.4.15 Verbenaceae
15.4.16 Umbelliferae
15.4.17 Zingiberaceae
15.5 Synergistic Formulations by Combination of Antimicrobials and Essential Oils to Reverse Resistance
15.6 Concluding Remarks
References
16: Bacterial Drug Efflux Pump Inhibitors from Plants
16.1 Introduction
16.2 Bacterial Efflux Pump Systems: An Overview
16.2.1 Background
16.2.2 Classification and Physiology of Efflux Pump Systems
16.2.2.1 Families of Drug Efflux Pumps
16.2.2.2 Structure of Drug Efflux Pumps
16.2.2.3 Energy Sources of Drug Efflux Pumps
16.2.2.4 Substrate Recognition
16.2.2.5 Mechanisms of Drug Efflux
16.2.2.6 Specificities of Efflux Pump Families
ATP-Binding Cassette (ABC) Superfamily
Major Facilitator Superfamily (MFS)
Small Multidrug Resistance (SMR) Family
Multidrug and Toxic Extrusion (MATE) Family
Resistance-Nodulation-Cell Division (RND) Superfamily
16.2.3 Public Health Significance of Multidrug Efflux Pumps
16.3 Efflux Pump Inhibitors (EPIs)
16.3.1 EPIs as Promising Therapeutic Agents to Reverse Bacterial MDR
16.3.2 Properties of an Effective Efflux Pump Inhibitor
16.3.3 Classification of Efflux Pump Inhibitors
16.3.3.1 Classes of Efflux Pump Inhibitors Based on their Mechanisms of Action
Energy Dissipation
Direct Binding Inhibition
16.3.3.2 Classes of EPIs Based on their Origin
EPIs Originated from Plants
EPIs Originated from Microorganisms
EPIs Originated from Chemical Synthesis
16.4 Methods of Screening Efflux Pump Inhibitors
16.4.1 Direct Measurement of Efflux Activity
16.4.2 Accumulation Assay
16.5 Efflux Pump Inhibitors (EPIs) from Plants
16.5.1 Terpenoids
16.5.2 Phenolic Compounds
16.5.3 Alkaloids
16.6 Drugs from Plant-Derived EPIs: Current Stage and Challenges in Drug Development and Clinical Use
16.6.1 Current Stage of Development of Plant-Derived EPI Drugs
16.6.2 Current Challenges in the Development and Clinical Use of Plant-Derived EPI Drugs
16.7 Future Perspectives
16.8 Conclusion
References
17: Anti-Quorum Sensing Agents from Natural Sources
17.1 Introduction
17.2 Overview on Quorum Sensing
17.2.1 Quorum Sensing in Gram-Positive Bacteria
17.2.2 Quorum Sensing in Gram-Negative Bacteria
17.3 Quorum Quenching of Bioactive Compounds from Medicinal Plants
17.3.1 Quorum Quenching of Terpenes
17.3.2 Quorum Quenching of Flavonoids
17.3.3 Quorum Quenching of Phenolic Acids
17.4 Conclusion
References
18: Plant-Assisted Plasmid Curing Strategies for Reversal of Antibiotic Resistance
18.1 Introduction
18.2 Why Target Plasmids?
18.3 Strategies for Removing MGEs
18.3.1 Elimination of Plasmid
18.3.2 Inhibition of Conjugation
18.4 Biological Strategies for Elimination of MGEs
18.5 Nanoparticles in Plasmid Curing
18.6 CRISPR-Cas9-Based Approach to Plasmid Curing
18.7 Stress-Free Strategy to Cure Plasmid
18.8 Rationale for the Use of Plant Resources in Drug Resistance Reversal
18.9 Plant-Derived Plasmid Curing Agents
18.10 Plant Extracts in Plasmid Curing/Conjugal Inhibition
18.11 Plant-Assisted Nanoparticles as Plasmid Curing Agents
18.12 Future of Plant-Assisted Curing Agents
References
19: Natural Product as Efflux Pump Inhibitors Against MRSA Efflux Pumps: An Update
19.1 Introduction
19.2 Screening of Efflux Pump Inhibitors
19.2.1 Accumulation Assay (EtBr or Berberine)
19.2.2 Susceptibility Testing
19.2.3 MIC Synergy Testing in the Presence of EPI
19.2.4 Fractional Inhibitory Testing (FIC)
19.2.5 Time Kill Studies
19.2.6 Natural Product Inhibitors of Efflux Pumps
19.2.6.1 S.aureus NorA Multidrug Efflux Pump Inhibitors
19.2.7 Polyphenols
19.2.7.1 2-Arylbenzofuran
19.2.7.2 N-Caffeoylphenylkylamides
19.2.7.3 Caffeoylquinic Acids
19.2.7.4 Terpenoids
19.2.7.5 Oligosaccharides
19.2.7.6 Alkaloids
19.2.7.7 Miscellaneous NorA EPIs
19.2.7.8 MsrA Efflux Pump Inhibitors of Natural Product Origin
19.2.7.9 Miscellaneous S. aureus and MRSA Efflux Pump Inhibitors of Natural Product Origin
19.3 Concluding Remarks
References