Pathogenicity and Drug Resistance of Human Pathogens: Mechanisms and Novel Approaches

Foreword
Foreword
Preface
Contents
Editors and Contributors
	About the Editors
	Contributors
Part I: Pathogenicity and Drug Resistance in Mycobacterium tuberculosis
	Molecular Basis of Drug Resistance in Mycobacteria
		Resistance Due to Common Mechanisms like Permeability and Efflux Pumps
		Molecular Mechanism(s) Associated with/Contributing to Resistance Against Different Groups of Antimycobacterial Drugs
		Rifamycins
			Leprosy
			NTM
			Rifamycin Congeners
		Isoniazid (INH)
		Ethionamide/Prothionamide
		Pyrazinamide (PZA)
		Ethambutol (EMB)
		Aminoglycosides
		Cyclic Peptide Antibiotics
		Clofazimine (CLF)
		Bedaquiline (Bdq)
		Delaminid
		Linezolid (LZD)
		Cycloserine
		Terizidone (TRD)
		Fluoroquinolones (FQs)
			FQ Resistance in Mycobacterium tuberculosis
			FQ Resistance in M. leprae
		Macrolides
		Sulphones
		Para-amino Salicylic Acid (PAS)
		Beta-lactam Antibiotics
		Tetracyclines (TET)
		Future Perspective
		References
	The Challenge of Drug-Resistant Tuberculosis: An Update
		Introduction
		Drug-Resistant TB: Magnitude of the Problem
			The Global Burden of MDR-TB
		Risk Factors for Development of Drug-Resistant TB
		Mechanisms of Antituberculosis Drug Resistance and Factors Associated with Its Emergence
			Mechanism of Resistance to First-Line Anti-TB Drugs (Table 1)
				Rifampicin (RIF)
				Isoniazid (INH)
				Pyrazinamide (PZA)
				Ethambutol (EMB)
			Fluoroquinolones (Group A)
			Second-Line Injectable Drugs (Group B)
				Streptomycin (SM)
				Kanamycin (KAN) and Amikacin (AMK)
			Other Core Second-Line Drugs (Group C)
				Clofazimine (CFZ)
				Ethionamide (ETH)
				D-Cycloserine (DCS)
				Para-aminosalicylic Acid (PAS)
			Recently Introduced Anti-TB Drugs
				Bedaquiline (BDQ)
				Delamanid
			Alternative Mechanisms of Drug Resistance
				Membrane Impermeability
				Drug Inactivation or Modification by Enzymes
				Target Alteration
			Drug Resistance in M. tuberculosis Is Very Complex and Some Other Complicating Factors Should Also Be Considered
				Drug Tolerance and Persistence
				Cross-Resistance
				Hetero-resistance
		Detection of Drug-Resistant M. tuberculosis
			Phenotypic Drug Susceptibility Testing (PDST) Methods
				Absolute Concentration Method
				Resistance Ratio Method
				Proportion Method of Drug Susceptibility Testing (PDST)
				Nitrate Reductase Method
				Microscopic Observation Drug Susceptibility (MODS)
				Mycobacteria Growth Indicator Tube (MGIT)
			Molecular and Genotypic Methods
				Line Probe Assay
				GeneXpert
				Whole Genome Sequencing (WGS)
		References
	Eliminating Mycobacterial Persistence: Novel Targets for Anti-TB Therapy
		Introduction
		Dormant Bacilli
		Persisters
		Latent Bacteria
		Models for Studying Dormancy, Persistence, and Latency
			In Vitro Models
				The Wayne Model
				Nutrient Starvation Model
				Single Stress Models
				Multiple Stress Model
				Persister Model
			In Vivo Models
				Cornell Mouse Model
				Guinea Pig/Rabbit Model
				Nonhuman Primate Model
		Mechanisms of Mycobacterial Persistence
			Metabolic Adaptations
				Glyoxylate Shunt and Gluconeogenesis
				Nitrate Respiration
			Regulatory Mechanisms
				Stringent Response
				Dos Regulon
				Toxin-Antitoxin Modules
				Transcription Factors
			Other Mechanisms
				Efflux Pumps
				Cell Wall Components
		Strategies to Target Latent TB
			Targeting Resuscitation-Promoting Factors (Rpf)
			Anti-persister Strategies
			Alternative Treatment Strategies
		Concluding Remarks
		References
	Response of Mycobacterium tuberculosis to pH Stress: Promising Approach to Control Tuberculosis
		Introduction
		Significance of pH in MTB Pathogenesis
		Factors Governing pH Responses in MTB
			Cell Envelope
			Porins
			Carbon Sources
			β-Carbonic Anhydrase
			Protonophores
			Proteases
			Transcriptional Regulator
			Micronutrients
				Potassium
				Magnesium
		Targeting pH Homeostasis as Promising Approach
			Targeting Cell Envelope
			Targeting Porins
			Targeting Carbon Sources
			Targeting β-Carbonic Anhydrase
			Targeting Protonophores
			Targeting Proteases
			Targeting Transcriptional Regulator
			Targeting Micronutrients
		Conclusión
		References
	Roadmap for the Eradication of Multidrug Resistant Tuberculosis
		Introduction
		Global Efforts to Control and Eliminate TB
		Control, Elimination and Eradication
		Case Finding
		Diagnosis of TB and Future Prospects
		Latent Tuberculosis Infection
		TB Vaccine
		TB Drugs and Regimens
		TB Elimination in India
		Conclusion
		References
Part II: Candida Infections and Therapeutic Strategies
	Fungal Diseases and Their Treatment: A Holistic Approach
		Introduction
		Fungi
			Type of Fungi
		How Fungi Interact with Human?
		Pathogenesis of Fungi
		Sources of Fungal Infections
		Type of Infections Caused by Fungal Pathogens
			Fungal diseases on the basis of site of infection in the human body
		How Common Are Fungal Diseases?
			Infection on the Basis of Affected Organs of the Human Body
		Epidemiology of Pathogenic Fungi
		Current Trends of Available Drugs against Fungi
		Multidrug Resistance in Pathogenic Fungi
		Mechanisms of Drug Resistance in Fungi
		Ways to Overcome Drug Resistance of Fungi
		Future Directions of the Drugs Against Resistance Fungi
		Conclusions
		References
	Candida Pathogenicity and Alternative Therapeutic Strategies
		Introduction
			C. albicans and Other Candida Species
			Virulence and Pathogenicity
			Conventional Antifungal Drugs and Their Mode of Action
			Phytomedicine and New Approaches
		Conclusion
		References
	Role of Mitochondria in Fungal Drug Resistance
		Introduction
		Mitochondrial Genome in Different Fungi
		Role of Mitochondria in Drug Resistance
			Importance of mtDNA and Mitochondria Dysfunction in Drug Resistance
			Heme metabolism affecting Resistance/Sensitivity
			Endoplasmic Reticulum (ER)-Mitochondrial Calcium (Ca2+) Crosstalk
			Mitochondria association with ER
			Phospholipid Biosynthesis in Mitochondria
			Others
		Concluding Comments
		References
	Preventive Potential and Action Mechanism of Essential Oils Against Dermatophytes
		Introduction
		The Diseases Caused by Dermatophytes
		Essential Oils in Control of Dermatophytic Problems
		Antidermatophytic Potential of Essential Oils
		Essential Oils Mechanism of Action on Dermatophytes
		Conclusions
		References
Part III: Malaria Parasite Biology
	Road Towards Development of New Antimalarial: Organelle Associated Metabolic Pathways in Plasmodium as Drug Targets and Discov...
		Introduction
		Antimalarials Targeting Haemoglobin Uptake, Degradation and the Food Vacuole
		Mitochondrial Metabolic Pathways as Targets for Anti-malarial Development
			Electron Transport Chain (ETC)
			Components of TCA Cycle
			Pyrimidine Biosynthesis Pathway
			Protein Synthesis and Degradation Pathways in Mitochondria
			Fe-S Cluster Biosynthesis
		Metabolic Pathways in Apicoplast for Antimalarial Development
			Apicoplast-Associated Fatty Acid Biosynthesis
			Isoprenoids Biosynthesis as Target and Use of Antibiotics
			Inhibitors of Transcription and Translation Machinery in the Apicoplast
			Heme Biosynthesis
			Iron-Sulphur (Fe-S) Biosynthesis
			Apicoplast Proteases
		Lipid Metabolism in Plasmodium: Potential Targets for Drug Development
		Recent Developments in Antimalarial Discovery
		Summary
		References
	Cellular Homoeostasis and Cell Signalling in Malaria Parasite: Role of Autophagy
		Introduction
		Autophagy and Signalling in Plasmodium
		Induction and Nucleation of Autophagosome Vacuoles
			Atg1 Kinase Complex
			ATG9 and Its Cycling System
			Atg8 and Atg12 Ubiquitin Conjugation System
			Atg7 Protein Complex
			PtdIns3K Complex
		Phagophore Expansion
		Roles of Autophagy in Plasmodium
		Autophagy in Protein Secretion and Trafficking
		Autophagy in Programmed Cell Death
		Host Autophagy Machinery During Plasmodium Life Cycle
		References
Part IV: Emerging Viral Diseases
	Hepatitis C Virus and Innate Interferon Response: Pathogen Biology, Drug Resistance, Novel Drug Targets, and Therapeutic Strat...
		Introduction
		HCV Biology and Pathogenesis
		HCV Genome Sensing and Innate Immune System
			HCV Genome Recognition by Retinoic Inducible Gene-I
			HCV Genome Recognition by MDA5
			HCV Genome Recognition by TLRs
		Downstream Signaling from TLR3, TLR7, and TLR8
		HCV Infection and Induction of Interferons
		Viral Proteins Known to Block Interferon Response
		Role of Other Sensing Molecules in Interferon Response Against HCV
		Novel Drugs and Therapeutic Strategies
		Antiviral Drug Resistance
		Conclusion
		References
	Epidemiological Trends and Current Challenges in Ebola: Pathogen Biology, Drug Targets, and Therapeutic Strategies
		Ebola Virus Characteristics Taxonomy, Morphology, and Structure
		Transmission Among Humans
		Genetics Genome, Gene Functions, Transcription, and Replication
		Evolution
		Biology of Virus Entry and Multiplication in Host Cells
		Drug Targets and Therapeutics
		Inhibitors of Ebola Virus Entry
		Replication of EBOV
		Interferons
		EBOV Gene Expression Inhibitors
		Other Therapeutic Strategy: Transfusion of Convalescent Blood/Serum
		Small Molecules as Inhibitors of Ebola Virus Infection
		Repurposed Drugs
		Challenges and Prospects
		References
	Prion Diseases: A Concern for Mankind
		Introduction
		Discovery of Prions
		Prion Proteins
		Pathogenesis of Human Prion Diseases
		Cell-to-Cell Spread of Prion Proteins
		Toxicity of Prion Protein Aggregates
		Transmission of Prion Proteins
			``Natural´´ Transmissions
			Iatrogenic/Accidental Transmission (iCJD)
		Geographical Distribution of Human Prion Disease
		Prion Diseases: Clinical Features and Molecular Diagnosis
			sCJD
			gCJD
			Acquired CJD
				Kuru
				vCJD
				iCJD
		Treatment
		Vaccination
		Infection Control and Prevention
		References
Part V: Translational Research in Human Microbes
	Harnessing Microbiota as Anti-infectives
		Introduction
		Probiotic Microorganisms
		Selection Criteria and Characteristics for Ideal Probiotic Microorganisms
		Mechanism of Action
		Vehicles
		Health Benefits Through Probiotics
			Prevention and/or Reduction of Diarrhea
			Lactose Intolerance
			Calcium Absorption
			Reduction of Concentration of Cancer by Promoting Enzymes in the Gut
			Immune Response
			Prevention or Alleviation of Allergies and Atopic Diseases in Infants
			Cancer Prevention
			Prevention of Heart Diseases/Influence on Blood Cholesterol Levels
		Conclusion
		References
	Human Microbiome and Malignancy: Principles, Mechanisms, and Challenges
		Introduction
			Human Microbiome
			The Human Microbiome: Dynamic Interactions, Diversity, and Role in Digestion and Nutrition
			The Human Microbiome and Disease
		Human Microbiome and Cancer
			Oncogenic Microbes: Classification, Principles, and Mechanisms of Microbial Oncogenesis
			Oncogenic Microbes: Nonviral Oncogenesis
				Parasites, Fungus, and Bacteria
				Oncogenic Microbes: Viral Oncogenesis
					Human T-Cell Leukemia Virus
					Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV)
					Human Papillomavirus (HPV)
			Association of Microbiome with Cancer: Mechanistic Studies
		Conclusions
		References
	Nanobiotechnology: Current and Future Perspectives in Combating Microbial Pathogenesis
		Introduction
		Nanobiotechnology in Microbiology
		Nanobiotechnology in Agriculture
		Nanobiotechnology in Environmental Activity
		Nanobiotechnology in Medical Microbiology
		Nanobiotechnology in Food Microbiology
		Impact of Different Forms of Nanofabricated Structures on Microbial Growth
			Anti-biofilm Agents
			Bacteriophage Template for Nanostructures
			Biosensors
			Quantum Dots
			Bacterial Magnetic Nanoparticles (BMPs)
			Nanobiotechnological Techniques for Enzyme Hybridization
			Nanorobots
			Nanoparticles as Microbe Combating Agents
		Future Aspect of Nanobiotechnology Use in Combating Microbial Diverse Population
		Conclusion
		References
	Microbes in the Reproductive Tract Spectrum: Inferences from the Microbial World
		Introduction
		Overview of the Reproductive System
			Male Reproductive Organs
			Female Reproductive Organs
		Types of RTIs
			Sexually Transmitted Diseases
				STDs Caused by Bacteria
					Bacterial Vaginosis
					Chlamydia
					Gonorrhea
					Syphilis
				STDs Caused by Protozoa
					Trichomoniasis
				STDs Caused by Fungus
					Genital Candida
				STDs Caused by Virus
					Human Papilloma Virus or Genital Warts (HPV)
					Human Immunodeficiency Virus (HIV)
					Genital Herpes
			Endogenous Infections
			Iatrogenic Infections
		General Concerns Related to RTIs
		Management and Preventive Measures for RTI
			Management
				Drug Resistance
			Prevention
				Prevention for STIs
				Prevention for Endogenous Infections
				Prevention for Iatrogenic Infections
		Future Perspective
		Conclusion
		References
	Discovery of Novel Drug Targets in Microbial Pathogens Among Hypothetical Proteins: Methods and Significance
		Introduction
			Associated Diseases
			Current Status
			Hypothetical Proteins
			In Silico Function Prediction of Hypothetical Proteins
		Common Indian Bacterial Pathogens
			Mycobacterium tuberculosis
			Mycoplasma pneumoniae
			Treponema pallidum
			Chlamydia trachomatis
			Helicobacter pylori
			Mycobacterium leprae
			Haemophilus influenzae
			Neisseria gonorrhoeae
		Hypothetical Proteins
			What Is Hypothetical Protein?
			Relevance and Importance of Hypothetical Proteins
		In Silico Function Prediction of Hypothetical Proteins
			Sequence-Based Function Prediction of the HPs
				Similarity Search Methods
				Classification Methods
				Protein-Protein Interaction Networks for Function Prediction
				Physicochemical Properties and Subcellular Localization
				Prediction of Virulence Factors
			Structure-Based Function Prediction of the HPs
		Consensus-Based Function Prediction
		Conclusions
		References
	Microbial Natural Products: Exploiting Microbes Against Drug-Resistant Bugs
		Introduction
			Microbe-Derived Antimicrobials and Their Mode of Action
		Conclusion
		References