ESKAPE Pathogens: Detection, Mechanisms and Treatment Strategies

Preface
Contents
Editors and Contributors
About the Editors
Contributors
1: Medical Importance of ESKAPE Pathogens
	1.1	 Introduction
		1.1.1	 ESKAPE Pathogens and Nosocomial Infections
	1.2	 ESKAPE Organisms and Pathogenic Concerns
		1.2.1	 Enterococcus faecium
		1.2.2	 Staphylococcus aureus
		1.2.3	 Klebsiella pneumoniae
		1.2.4	 Acinetobacter baumannii
		1.2.5	 Pseudomonas aeruginosa
		1.2.6	 Enterobacter Species
	1.3	 Major Nosocomial Infections by ESKAPE Pathogens
		1.3.1	 Bloodstream Infection (BSI)
		1.3.2	 Ventilator Associated Pneumonia (VAP)
		1.3.3	 Urinary Tract Infection (UTI)
		1.3.4	 Surgical Site Infections (SSI)
	1.4	 Prevalence of ESKAPE Pathogens in Environment
	1.5	 Antibiotic Resistance in ESKAPE Organisms
		1.5.1	 Alteration/Modification of Drugs
			1.5.1.1	 Hydrolase Enzymes
			1.5.1.2	 Aminoglycoside-Modifying Enzymes
		1.5.2	 Alteration of Drug Target Sites
			1.5.2.1	 Target Enzyme Alteration
			1.5.2.2	 Modification of Ribosomal Target
			1.5.2.3	 Modifications in Cell Wall Precursors
		1.5.3	 Inhibition of Drug Influx and Accumulation
			1.5.3.1	 Efflux Pumps
		1.5.4	 Transmission of Resistant Strains and ARGs
	1.6	 Current Strategies to Compete Against ESKAPE Pathogens
	1.7	 Conclusion
	References
2: Antibiotic Resistance Profile and Detection in ESKAPE Pathogens
	2.1	 Introduction
		2.1.1	 ESKAPE Pathogens and Their Significance
		2.1.2	 Antibiotic Resistance in ESKAPE Pathogens
	2.2	 Antibiotic Resistance Mechanism in ESKAPE Pathogens
		2.2.1	 Antibiotic Inactivation by Enzyme Production
		2.2.2	 Alterations of Membrane Permeability
		2.2.3	 Alterations in Antibiotic-Target Sites
		2.2.4	 Efflux Pump Activation
	2.3	 Antibiotic Resistance Profile in ESKAPE Pathogens
		2.3.1	 Antibiotic Resistance Profile of Acinetobacter baumannii
		2.3.2	 Antibiotic Resistance Profile of Pseudomonas aeruginosa
		2.3.3	 Antibiotic Resistance Profile of Klebsiella pneumoniae
		2.3.4	 Antibiotic Resistance Profile of Enterobacter Species
		2.3.5	 Antibiotic Resistance Profile of Staphylococcus aureus
		2.3.6	 Antibiotic Resistance Profile of Enterococcus faecium
	2.4	 Detection Methods for Antibiotic Resistance in ESKAPE Pathogens
		2.4.1	 Different Detection Tools Used for Antibiotic Resistance Profiling
			2.4.1.1	 Conventional Detection Methods
			2.4.1.2	 Non-Conventional Detection Methods
			2.4.1.3	 Emerging Detection Methods
	2.5	 Conclusion
	References
3: Mechanistic Understanding of Antibiotic Resistance in ESKAPE Pathogens
	3.1	 Introduction
	3.2	 Overview of Antibiotic Resistance in ESKAPE Pathogens
		3.2.1	 E. faecium
		3.2.2	 S. aureus
		3.2.3	 K. pneumoniae
		3.2.4	 A. baumannii
		3.2.5	 P. aeruginosa
		3.2.6	 Enterobacter spp.
	3.3	 Impact of Antibiotic Resistance on Treatment Options
	3.4	 Mechanisms of Antibiotic Resistance in ESKAPE Pathogens
		3.4.1	 Production of Enzymes That Inactivate or Alter Antibiotics
			3.4.1.1	 Beta-Lactamases
			3.4.1.2	 AMEs
			3.4.1.3	 Aminoglycoside N-Acetyltransferases (AACs)
			3.4.1.4	 Aminoglycoside O-Phosphotransferases (APHs)
			3.4.1.5	 Aminoglycoside O-Nucleotidyltransferase (ANTs)
			3.4.1.6	 Chloramphenicol Acetyltransferases
			3.4.1.7	 Macrolide Esterases and Phosphotransferase
		3.4.2	 Modification of Antibiotic Target Site
		3.4.3	 Replacement of Original Target Enzymes
		3.4.4	 Binding Site Modification of Antibiotics
		3.4.5	 Chemical Modification of Cell Wall Composition
		3.4.6	 Decreased Antibiotic Invasion and Subcellular Accumulation
		3.4.7	 Reduced Antibiotic Uptake
		3.4.8	 Increased Efflux of Antibiotics
		3.4.9	 Altered Cell Wall or Membrane Composition (Biofilm Formation)
		3.4.10	 Persister Cells and Antibiotic Tolerance
	3.5	 Intracellular Survival Mechanism of Antibiotic Resistant Pathogens
	3.6	 Genetic Determinants of Resistance
		3.6.1	 IS and Tns
		3.6.2	 Plasmids
			3.6.2.1	 Transferability
			3.6.2.2	 Co-Resistance
			3.6.2.3	 Plasmid Size and Replicon Types
			3.6.2.4	 Evolution and Adaptation
		3.6.3	 GIs and ICEs
	3.7	 HGT and Resistance Spread
	3.8	 Role of Antibiotic Use and Misuse
	3.9	 Novel Therapeutic Targets
	3.10	 Alternative Therapies
		3.10.1	 Bacteriophage Therapy
		3.10.2	 Antimicrobial Peptides (AMPs)
		3.10.3	 Probiotics
		3.10.4	 Immunotherapies
		3.10.5	 Photodynamic Therapy (PDT)
		3.10.6	 Essential Oils and Plant Extracts
		3.10.7	 Nanoparticles
	3.11	 Future Directions for Research and Interventions
	3.12	 Conclusion
	References
4: Standard Microbiological Techniques (Staining, Morphological and Cultural Characteristics, Biochemical Properties, and Serotyping) in the Detection of ESKAPE Pathogens
	4.1	 Introduction
	4.2	 Microbial Staining Techniques
		4.2.1	 Gram Staining
			4.2.1.1	 Golden Standard Procedure for Gram Staining
		4.2.2	 Limitations and Troubleshooting Staining Techniques of ESKAPE Pathogens
	4.3	 Morphological and Cultural Characteristics
		4.3.1	 Key Morphological and Cultural Characteristics of ESKAPE Pathogens
		4.3.2	 Limitations and Troubleshooting in Cultural Characteristics of ESKAPE Pathogens
	4.4	 Biochemical Properties
		4.4.1	 Major Biochemical Tests for the Detection of ESKAPE Pathogens
			4.4.1.1	 Catalase Test
			4.4.1.2	 Oxidase Test
			4.4.1.3	 Urease Test
			4.4.1.4	 Gelatin Hydrolysis Test
			4.4.1.5	 Nitrate Reduction Test
			4.4.1.6	 Methyl Red Test
			4.4.1.7	 Voges–Proskauer Test
			4.4.1.8	 Citrate Test
			4.4.1.9	 Carbohydrate Utilization Test
		4.4.2	 Limitations of Biochemical Tests
		4.4.3	 Recent Advancements in Biochemical Analyses
	4.5	 Serotyping
		4.5.1	 Serological Agglutination Test
		4.5.2	 Molecular Serotyping
	4.6	 Future Perspectives
	4.7	 Conclusion
	References
5: Nucleic Acid Amplification and Molecular Diagnostic Techniques in the Detection of ESKAPE Bacterial Pathogens
	5.1	 Bacterial Pathogens of ESKAPE
		5.1.1	 Enterococcus faecium
		5.1.2	 Staphylococcus aureus
		5.1.3	 Klebsiella pneumonia
		5.1.4	 Acinetobacter baumannii
		5.1.5	 Pseudomonas aeruginosa
		5.1.6	 Enterobacter Species
	5.2	 Diseases Associated with ESKAPE Bacterial Pathogens
	5.3	 Currently Available Diagnostic Techniques to Identify the ESKAPE Bacterial Pathogens
		5.3.1	 Molecular Diagnostic Techniques Used for Detection
		5.3.2	 Polymerase Chain Reaction (PCR)
		5.3.3	 DNA Microarray
	5.4	 Nucleic Acid Amplification and Importance in Diagnosis of ESKAPE Pathogens
	References
6: Biochemical, Molecular, and Computational Techniques for the Determination of Virulence Factors of ESKAPE Pathogens
	6.1	 Introduction
	6.2	 Virulence Factors
		6.2.1	 Enterococcus faecium (E. faecium)
		6.2.2	 Staphylococcus aureus (S. aureus)
		6.2.3	 Klebsiella pneumoniae (K. pneumoniae)
		6.2.4	 Acinetobacter baumannii (A. baumannii)
		6.2.5	 Pseudomonas aeruginosa (P. aeruginosa)
		6.2.6	 Enterobacter Species
	6.3	 Biochemical, Molecular, and Computational Techniques for the Identification of Virulence Factors of ESKAPE Pathogens
		6.3.1	 Biochemical Methods
			6.3.1.1	 Traditional Methods
			6.3.1.2	 Matrix-Assisted Laser Desorption Ionization Time Flight Mass Spectrometry (MALDI-TOF MS)
			6.3.1.3	 Microfluidics
		6.3.2	 Molecular Methods
			6.3.2.1	 Polymerase Chain Reaction (PCR)
			6.3.2.2	 Real-Time PCR (RT-PCR)
			6.3.2.3	 BioFire FilmArrays
			6.3.2.4	 DNA Microarrays
			6.3.2.5	 Pulse Field Gel Electrophoresis (PFGE)
			6.3.2.6	 Whole-Genome Sequencing (WGS)
			6.3.2.7	 Next-Generation Sequencing (NGS)
			6.3.2.8	 Biosensor
		6.3.3	 Computational Methods
			6.3.3.1	 PathoFact
			6.3.3.2	 Virulence Factor Databases and Servers
				6.3.3.2.1 MvirDB
				6.3.3.2.2 Virulence Factor Database (VFDB)
				6.3.3.2.3 VirulentPred
	6.4	 Conclusion
	References
7: Enterococcus faecium Virulence Factors and Biofilm Components: Synthesis, Structure, Function, and Inhibitors
	7.1	 Introduction
	7.2	 Virulence Factors
		7.2.1	 Virulence Factors (Secreted Nature)
		7.2.2	 Cell Surface Virulence Factors
	7.3	 Biofilm Formation
		7.3.1	 Biofilm Components
			7.3.1.1	 Polysaccharides
			7.3.1.2	 Lipids
			7.3.1.3	 Proteins
			7.3.1.4	 Nucleic Acids
		7.3.2	 Synthesis of Biofilm
			7.3.2.1	 Structure and Functions of Biofilm
	7.4	 Inhibitors
		7.4.1	 Quorum Sensing (QS)
		7.4.2	 Electrochemical Method for Degradation of Biofilm
		7.4.3	 Degradation of the EPS Matrix of Biofilm
		7.4.4	 External Membrane Structure
		7.4.5	 Enzyme-Mediated Biofilm Control
	7.5	 Conclusion
	References
8: Staphylococcus aureus Virulence Factors and Biofilm Components: Synthesis, Structure, Function and Inhibitors
	8.1	 Introduction
	8.2	 Virulence Factors
		8.2.1	 Capsular Polysaccharides
		8.2.2	 Cell Wall-Anchored (CWA) Proteins
			8.2.2.1	 Staphylococcal Protein A
			8.2.2.2	 Fibronectin (Fn)-Binding Adhesins (Fn-BPA & Fn-BPB)
			8.2.2.3	 Clumping Factors A and B (ClfA & ClfB)
			8.2.2.4	 Serine-Aspartate Repeat Protein (SdrC, SdrD and SdrE)
			8.2.2.5	 Collagen Adhesion Protein (Cna)
			8.2.2.6	 S. aureus Surface Protein X (SasX)
			8.2.2.7	 Iron-Regulated Surface Proteins (Isd)
		8.2.3	 Staphyloxanthins (STX)
		8.2.4	 Extracellular Enzymes
			8.2.4.1	 Coagulase
			8.2.4.2	 Staphylokinase
			8.2.4.3	 Staphylococcal Nuclease
			8.2.4.4	 Proteases
				8.2.4.4.1 Metalloprotease: Aureolysin (Aur)
				8.2.4.4.2 Cysteine Protease
				8.2.4.4.3 Serine Protease (SspA)
				8.2.4.4.4 Hyaluronidase
			8.2.4.5	 Lipase
		8.2.5	 Staphylococcus aureus Toxins
			8.2.5.1	 Pore-Forming Toxins (PFTs)
			8.2.5.2	 Phenol-Soluble Modulins
			8.2.5.3	 Exfoliative Toxins
			8.2.5.4	 Superantigens (Ags)
	8.3	 Staphylococcus aureus Biofilm
		8.3.1	 Components of Biofilm
		8.3.2	 Biofilm Formation
		8.3.3	 Genetic Regulation in Biofilm Formation and Dispersal
	8.4	 Regulation of Virulence Factors
		8.4.1	 Accessory Gene Regulator (Agr) System
		8.4.2	 Staphylococcal Accessory Regulator (sar) System
		8.4.3	 Repressor of Toxins (Rot) System
		8.4.4	 Multiple Antibiotic Resistance Regulator (MgrA) System
		8.4.5	 Staphylococcus aureus Exoprotein (sae) System
		8.4.6	 Sigma Factor-Dependent Regulation
		8.4.7	 Staphylococcal Respiratory Regulator (SrrAB) System
	8.5	 S. aureus in Antimicrobial Drug Resistance
		8.5.1	 Evolutionary Origin of Multi-Drug-Resistant Staphylococcus aureus (MRSA, VRSA)
		8.5.2	 Mechanism of Antibiotic Resistance S. aureus
	8.6	 Inhibitors and Novel Therapeutics for S. aureus Infection
	8.7	 Conclusion
	8.8	 Future Prospective
	References
9: Klebsiella pneumoniae Virulence Factors and Biofilm Components: Synthesis, Structure, Function, and Inhibitors
	9.1	 Introduction
	9.2	 Klebsiella pneumoniae: A Potent ESKAPE Pathogen
	9.3	 Virulence Factors: Structure and Its Function
		9.3.1	 Capsular Polysaccharides (CPS)
		9.3.2	 Lipopolysaccharides
		9.3.3	 Fimbriae and Pili
		9.3.4	 Iron Acquisition Systems (Siderophores)
		9.3.5	 Toxin
	9.4	 Biofilm Formation by Klebsiella pneumoniae
		9.4.1	 Factors Contributing Biofilm Formation
		9.4.2	 Regulation of Biofilm Formation
	9.5	 Importance of Biofilm Formation in Klebsiella pneumoniae Pathogenesis
	9.6	 Function and Role of Klebsiella pneumoniae Virulence Factors and Biofilm Components
	9.7	 Host-Pathogen Interactions
	9.8	 Immune Evasion Strategies
	9.9	 Impact on Disease Progression and Severity
	9.10	 Inhibition of K. pneumoniae Virulence Factors and Biofilm Formation
		9.10.1	 Current Approaches and Strategies
		9.10.2	 Small Molecule Inhibitors
		9.10.3	 Antibodies and Vaccines
	9.11	 Future Directions and Challenges
	9.12	 Conclusion
	References
10: Acinetobacter baumannii Virulence Factors and Biofilm Components: Synthesis, Structure, Function, and Inhibitors
	10.1	 Introduction
	10.2	 Acinetobacter baumannii Infection
	10.3	 A. baumannii: An Emerging Hospital-Associated Pathogen and Colonizer
	10.4	 Antimicrobial Resistance of A. baumannii
	10.5	 Quorum Sensing
		10.5.1	 Quorum Sensing in Gram-Negative Bacteria
		10.5.2	 Quorum-Sensing System in A. baumannii
		10.5.3	 Biofilm Formation in A. baumannii
		10.5.4	 Biofilm Development
		10.5.5	 Arsenal of QS-Controlled Virulence Factors Deployed by A. baumannii
			10.5.5.1	 Outer Membrane Proteins (OMPs) and Inhibitors
			10.5.5.2	 Biofilm-Associated Arsenal Virulence Factors and Inhibitors
				Pili/Fimbriae and Inhibitors
				Lipopolysaccharide
					Biosynthesis of Lipopolysaccharide and Inhibitors
					Capsular Polysaccharides and Exopolysaccharide
	10.6	 Pathogenesis of Acinetobacter baumannii Infections
	10.7	 Quorum-Sensing Inhibitors
	10.8	 Conclusion
	References
11: Pseudomonas aeruginosa Virulence Factors and Biofilm Components: Synthesis, Structure, Function and Inhibitors
	11.1	 Pseudomonas aeruginosa: An Overview
	11.2	 Virulence Factors of P. aeruginosa
	11.3	 Surface Virulence Components
		11.3.1	 Type IV Pili (T4P)
		11.3.2	 Flagella
		11.3.3	 Lipopolysaccharide (LPS)
		11.3.4	 Outer-Membrane Vesicles (OMVs)
	11.4	 Secretion Systems
		11.4.1	 Type I Secretion System (T1SS)
		11.4.2	 Type II Secretion System (T2SS)
		11.4.3	 Type III Secretion System (T3SS)
		11.4.4	 Type V Secretory System (T5SS)
		11.4.5	 Type VI Secretion System (T6SS)
	11.5	 Secreted Virulence Phenotypes
		11.5.1	 Exopolysaccharides (EPS)
		11.5.2	 Cytotoxins
			11.5.2.1	 Proteases
			11.5.2.2	 Siderophores
	11.6	 Biofilm Formation
	11.7	 Biofilm Matrix Components
		11.7.1	 Polysaccharides
			11.7.1.1	 Psl Polysaccharide
			11.7.1.2	 Pel Polysaccharide
			11.7.1.3	 Alginate
		11.7.2	 Extracellular DNA
		11.7.3	 Proteins
	11.8	 Virulence Factors and Biofilm Regulatory Mechanisms
		11.8.1	 Quorum Sensing
		11.8.2	 c-di-GMP
		11.8.3	 Two-Component System
	11.9	 Inhibitors of Virulence Factors and Biofilm
		11.9.1	 Phytochemicals
		11.9.2	 Small-Molecule Inhibitors
		11.9.3	 Antimicrobial Peptides
		11.9.4	 Bacteriophage Therapy
		11.9.5	 Photodynamic Therapy (PDT)
		11.9.6	 Nanoparticles
	11.10	 Conclusion
	References
12: Enterobacter spp. Virulence Factors and Biofilm Components: Synthesis, Structure, Function, and Inhibitors
	12.1	 Introduction
	12.2	 Enterobacter spp. as Opportunistic Pathogens
	12.3	 Virulence Factors of Enterobacter spp.
	12.4	 Biofilm Formation in Enterobacter spp.
	12.5	 Genes Involved in the Virulence Factor Production
	12.6	 Interaction Between VFs and Biofilm Components
	12.7	 Significance of Virulence Factors and Biofilms in Infections
	12.8	 Inhibition of Enterobacter spp. Biofilms
	12.9	 Conclusion
	References
13: Antibiotic Adjuvants and Their Synergistic Activity Against ESKAPE Pathogens
	13.1	 The Emerging Problem of Antibiotic Resistance
	13.2	 Mechanism of AMR in ESKAPE Pathogens
	13.3	 Need for New Drug Discovery
	13.4	 Antibiotic Adjuvants and Synergy
		13.4.1	 Beta-Lactamase Inhibitors
		13.4.2	 Inhibitors of Efflux Pumps (EPIs)
		13.4.3	 Membrane Permeabilizers
	13.5	 Antibiotic Adjuvants in Biofilm and Anti-Quorum Sensing Therapy
	13.6	 Clinical Improvements in Adjuvant Therapy
	13.7	 Conclusions
	References
14: Phytochemicals as Potential Antibacterial Agents Against ESKAPE Pathogens
	14.1	 Introduction
		14.1.1	 Antibiotics Against MDR Bacteria
		14.1.2	 Antibiotic Resistance: A Major Threat
		14.1.3	 AMR Profile in ESKAPE Pathogens
		14.1.4	 Biofilm-Related Drug Resistance in ESKAPE Pathogens
		14.1.5	 Quorum Sensing (QS) in ESKAPE Pathogens
		14.1.6	 Multidrug-Resistant Efflux Pump in ESKAPE Pathogens
		14.1.7	 Current Therapeutic Approaches Against ESKAPE Pathogens
	14.2	 Synthetic Drugs as Regulators of Bacterial Pathogenesis and Biofilm Mechanics
	14.3	 Antibacterial Properties of Phytochemicals
		14.3.1	 Mechanism of Antibacterial Properties
	14.4	 QS Modulation Mechanism by Phytochemicals
		14.4.1	 Potential Therapeutic Targets for Quorum Sensing (QS) Inhibition
		14.4.2	 Quorum Sensing (QS) Inhibition Mechanism
	14.5	 Regulatory Role of Phytochemicals on Biofilm Dynamics in ESKAPE Pathogens
		14.5.1	 Understanding the Mechanism of Biofilm Inhibition
	14.6	 Phytochemicals as Inhibitors of Efflux Pump in ESKAPE Pathogens
	14.7	 Phytochemicals-Based Nanoformulations for Antibacterial and Antibiofilm Applications
	14.8	 Recent Trends and Future Perspectives
	14.9	 Conclusion
	References
15: Applications of Photodynamic Therapy for the Eradication of ESKAPE Pathogens
	15.1	 Introduction
	15.2	 What Is an Antimicrobial Photodynamic Therapy (aPDT)
		15.2.1	 aPDT Mechanism and ROS Production
		15.2.2	 Types of Photosensitizers
		15.2.3	 Molecular Targets of aPDT
	15.3	 aPDT for Gram-Positive ESKAPE Pathogens
	15.4	 aPDT for Gram-Negative ESKAPE Pathogens
	15.5	 Animal Models to Study aPDT Against ESKAPE Pathogens
	15.6	 Future Perspectives and Conclusions
	References
16: Antimicrobial Peptides and Antibacterial Antibodies for the Elimination of ESKAPE Pathogens
	16.1	 Introduction
	16.2	 Peptide-Based Antibiotics
		16.2.1	 Overview of AMP Properties
		16.2.2	 Mechanisms of Action
			16.2.2.1	 Membrane Targeting Mechanisms
			16.2.2.2	 Non-membrane Targeting Mechanisms
	16.3	 Databases of Antimicrobial Peptides
	16.4	 Host Defense Peptides
	16.5	 α-Helical Peptides
	16.6	 Antibiofilm Peptides
	16.7	 Other Strategies
	16.8	 Enterococcus faecium-Specific AMPs
	16.9	 Acinetobacter baumannii-Specific AMPs
	16.10	 Klebsiella pneumonia-Specific AMPs
	16.11	 Pseudomonas aeruginosa-Specific AMPs
	16.12	 Staphylococcus aureus-Specific AMPs
	16.13	 AMPs Targeting Enterobacter Species
	16.14	 Future Perspective
	References
17: Antimicrobial Activity of Nanomaterials and Nanocomposites Against ESKAPE Pathogens
	17.1	 Introduction
	17.2	 Nanomaterials and Nanocomposites
		17.2.1	 Types of Nanomaterials and Nanocomposites Used in Antimicrobial Applications
		17.2.2	 Carbon-Based Nanomaterials
		17.2.3	 Polymer Nanomaterials
		17.2.4	 Mesoporous Silica Nanoparticles (MSNs)
		17.2.5	 Advantages of Using Nanomaterials and Nanocomposites for Antimicrobial Activity
	17.3	 Mechanisms of Antimicrobial Activity
		17.3.1	 Modes of Action of Nanomaterials and Nanocomposites Against ESKAPE Pathogens
		17.3.2	 Interaction of Nanomaterials and Nanocomposites with Bacterial Cells
		17.3.3	 Cell Membrane Interactions
	17.4	 Evaluation of Antimicrobial Activity
		17.4.1	 In Vitro Assessment Methods for Antimicrobial Activity
		17.4.2	 In Vivo Evaluation of Nanomaterials and Nanocomposites Against ESKAPE Pathogens
	17.5	 Synergistic Approaches
		17.5.1	 Enhanced Antimicrobial Activity Through Functionalization and Surface Modifications
		17.5.2	 Surface Charge Modification
		17.5.3	 Incorporation of Antibiotics
	17.6	 Safety and Toxicity Considerations
	17.7	 Future Directions and Challenges
	17.8	 Conclusion
	References
18: Bacteriophage Therapy to Combat ESKAPE Pathogens
	18.1	 Introduction
	18.2	 Pathogenicity of ESKAPE Pathogens
	18.3	 Novel Treatments Against ESKAPE Pathogens
	18.4	 Use of Bacteriophages
		18.4.1	 Bacteriophage Therapy Against Enterococcus faecium
		18.4.2	 Bacteriophage Therapy Against Acinetobacter baumannii
		18.4.3	 Bacteriophage Therapy Against Klebsiella pneumonia
		18.4.4	 Bacteriophage Therapy Against Pseudomonas aeruginosa
		18.4.5	 Bacteriophage Therapy Against Staphylococcus aureus
	18.5	 Adverse Effects of Bacteriophage Therapy
	18.6	 The Hurdle of Bacteriophage Delivery
	18.7	 Future of Bacteriophage Therapy
	References
19: Computational Approaches for the Inhibition of ESKAPE Pathogens
	19.1	 Introduction
		19.1.1	 A Brief Introduction to ESKAPE Pathogens
		19.1.2	 Chronic Bacterial Infections and Biofilm Dynamics in ESKAPE Pathogens
		19.1.3	 Therapeutics Against ESKAPE Pathogens
		19.1.4	 Drug Discovery and Conventional Drug Development Pipelines
	19.2	 Computational Approaches for Drug Discovery and Development
		19.2.1	 Computer-Aided Drug Designing (CADD)
			19.2.1.1	 Molecular Docking
			19.2.1.2	 Molecular Dynamics Simulation
			19.2.1.3	 De Novo Drug Design
			19.2.1.4	 Sequence-Based Virtual Screening (SVSBI)
			19.2.1.5	 Pharmacophore Modeling
			19.2.1.6	 Structure-Activity Relationship
	19.3	 Computational Tools for Drug Repurposing
	19.4	 Computational Tools for the Identification of Drugs Targeting ESKAPE Pathogens
		19.4.1	 Phytochemicals as Potent Inhibitors of Quorum Sensing and Biofilms Using Computational Approaches
		19.4.2	 Computational Tools for Identification of Microbial Secondary Metabolites Against ESKAPE Pathogens
	19.5	 Current Trends and Future Prospective
	19.6	 Conclusion
	References