Molecular Medical Microbiology

3rd Edition - November 14, 2023
Editors: Yi-Wei Tang, Musa Hindiyeh, Dongyou Liu, Andrew Sails, Paul Spearman, Jing-Ren Zhang
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 1 8 6 1 9 - 0
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 9 9 9 2 - 5

Molecular Medical Microbiology, Third Edition presents the latest release in what is considered to be the first book to synthesize new developments in both molecular and clinical… Read more

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Molecular Medical Microbiology, Third Edition presents the latest release in what is considered to be the first book to synthesize new developments in both molecular and clinical research. The molecular age has brought about dramatic changes in medical microbiology, along with great leaps in our understanding of the mechanisms of infectious disease. This third edition is completely updated, reviewed and expanded, providing a timely and helpful update for microbiologists, students and clinicians in the era of increasing use of molecular techniques, changing epidemiology and prevalence, and increasing resistance of many pathogenic bacteria.

Written by experts in the field, chapters include cutting-edge information and clinical overviews for each major bacterial group, along with the latest updates on vaccine development, molecular technology and diagnostic technology.

Cover image
Title page
Table of Contents
Copyright
List of contributors
About the editors
Preface
VOLUME 1
Chapter 1. Molecular medical microbiology—from bench to bedside
Abstract
1.1 The concept
1.2 The evolving concept
1.3 From bench to bedside
References
Part 1: Bacterial structure
Chapter 2. Classification of medically important bacteria
Abstract
2.1 Introduction
2.2 Basics of bacterial taxonomy
2.3 Gram-negative bacteria
2.4 Gram-positive bacteria
2.5 Conclusion and summary
References
Chapter 3. Bacterial ultrastructure
Abstract
3.1 Introduction
3.2 Overview of bacterial ultrastructures
3.3 Surface appendages
3.4 Flagella
3.5 Pili and fimbriae
3.6 Capsules and S-layers
3.7 Membrane vesicles
3.8 Bacterial cell walls
3.9 Gram-negative bacterial cell wall
3.10 Gram-positive bacterial cell walls
3.11 Mycobacteria
3.12 Cell wall-deficient bacteria
3.13 Cell walls of Archea and surface appendages
3.14 Cytoplasmic membrane
3.15 Nucleoid
3.16 Bacterial cell division
3.17 Cytoplasmic inclusions
3.18 Outlook
References
Chapter 4. Bacterial cell walls: peptidoglycan
Abstract
4.1 Introduction
4.2 The basic chemical structure of peptidoglycan
4.3 Biophysical properties of peptidoglycan
4.4 Architecture of peptidoglycan
4.5 Peptidoglycan biosynthesis and modifications
4.6 Covalent attachment of secondary cell wall polymers to peptidoglycan
4.7 Covalent attachment of proteins to peptidoglycan
4.8 Peptidoglycan synthesis during the cell cycle
Acknowledgments
References
Chapter 5. Bacterial capsules
Abstract
5.1 Introduction
5.2 Chemical and structural properties of the capsules
5.3 Genetics of capsule biosynthesis
5.4 Biosynthesis of the capsules
5.5 Regulation of capsule production
5.6 Biological functions of the capsules
5.7 The capsules as targets for host immunity and therapeutics
5.8 Conclusion and prospect
Acknowledgments
References
Chapter 6. Flagella
Abstract
6.1 Flagellar function
6.2 Flagellar structure
6.3 Phase variation
6.4 Filament structure
6.5 Filament helicity
6.6 Calladine model
6.7 Hook
6.8 Hook-associated proteins
6.9 Rod
6.10 The LP ring complex
6.11 The cytoplasmic ring
6.12 Flagellar protein export apparatus
6.13 Chaperones
6.14 The Mot proteins
6.15 Assembly system of flagella
6.16 Protein export apparatus
6.17 Morphological pathway
6.18 In the cytoplasm
6.19 In the periplasmic space
6.20 Outside the cell
6.21 Origin of flagella
6.22 Conclusion
Acknowledgment
References
Chapter 7. Bacterial pili and fimbriae
Abstract
7.1 Introduction
7.2 Chaperone-usher pathway pilus represented by type I fimbriae and P pilus of Escherichia coli
7.3 Type IV fimbriae and P pilus
7.4 Development of novel therapeutics via targeting the pilus biogenesis
7.5 Emerging themes and future directions
Acknowledgment
References
Chapter 8. Endospores, sporulation, and germination
Abstract
8.1 Introduction
8.2 Sporulation as a survival strategy
8.3 The endospore structure and resistance
8.4 Endospore formation
8.5 Spore awakening: germination
8.6 Endospore formers pathogens
8.7 Pathogenic spore formers control
8.8 Endospore detection
8.9 Endospore-based technology
References
Part 2: Bacterial cell function
Chapter 9. Bacterial growth and cultivation
Abstract
9.1 Introduction
9.2 Bacterial growth
9.3 Bacterial growth and antibiotics treatment
9.4 Bacterial cultivations
9.5 Final remarks
Acknowledgments
References
Chapter 10. Bacterial energy metabolism
Abstract
10.1 Introduction
10.2 Fermentation
References
Chapter 11. Biofilms, quorum sensing, and crosstalk
Abstract
11.1 Communal behavior of bacteria
11.2 A conceptual overview of quorum sensing
11.3 Quorum signals and circuits
11.4 Crosstalk or interkingdom signaling via quorum signals
11.5 How quorum signals modulate the immune response
11.6 Influence of mammalian hormones on bacterial virulence
11.7 Exploiting quorum sensing to treat disease
11.8 Biofilms as a cause of chronic infection
11.9 Biofilm development
11.10 Biofilm morphology
11.11 Biofilm metabolism
11.12 Biofilm tolerance
11.13 Conclusion
Acknowledgments
References
Chapter 12. Redox signaling mechanisms during host-pathogen interactions in the human pathogen Staphylococcus aureus
Abstract
12.1 Introduction to defense mechanisms against redox stress in Staphylococcus aureus
12.2 Generation of reactive oxygen, chlorine, and electrophile species
12.3 Posttranslational modifications of proteins by ROS, HOCl, and RES
12.4 Enzymatic pathways for detoxification of ROS, RCS, and RES in Staphylococcus aureus
12.5 The role of the low-molecular weight thiol bacillithiol in the ROS, RES, RCS, and antibiotics resistance
12.6 The role of the antioxidant pigment staphyloxanthin in S. aureus
12.7 Transcriptional regulators as redox sensors of ROS, RES, RCS, and O2 in Staphylococcus aureus
12.8 The Fur-family PerR repressor functions as metal-based peroxide sensor
12.9 The MarR-type redox-sensitive virulence regulators MgrA, SarZ, and SarA
12.10 The Rrf2-family HypR repressor functions as sensor of HOCl, HOSCN and oxidants
12.11 The MarR-family QsrR and MhqR repressors as sensors of quinones and oxidants
12.12 Role of the thiol-based redox sensor Spx and its YjbH adapter
12.13 The TetR-family GbaA repressor functions as monothiol electrophile sensor
12.14 The role of redox-sensing two-component systems in Staphylococcus aureus
12.15 The SrrAB two-component system regulates anaerobic respiration and fermentation
12.16 The NreABC two-component system controls nitrate respiration
12.17 The Rex redox-sensor senses the NADH/NAD+ ratio under anaerobic conditions
Acknowledgments
References
Chapter 13. Bacterial protein synthesis
Abstract
13.1 Ribosome and protein translation
13.2 Ribosome rescue system
13.3 Ribosome and antibiotic
Acknowledgments
References
Part 3: Bacterial genetics
Chapter 14. Bacterial chromosomes and their replication
Abstract
14.1 Introduction
14.2 Chromosome structure
14.3 Replication of the primary chromosome
14.4 Regulation of chromosome replication
14.5 Replication of chromids
14.6 Chromosome replication during infection
14.7 Perspective
References
Chapter 15. Mechanisms of horizontal gene transfer and DNA recombination
Abstract
15.1 Introduction
15.2 Transformation
15.3 Transduction
15.4 Conjugation
15.5 Homologous recombination
15.6 Site-specific recombination
15.7 Conclusions
References
Chapter 16. Pathogenicity islands: origins, structure, and roles in bacterial pathogenesis
Abstract
16.1 Pathogenicity islands: a type of genomic island
16.2 Organization of pathogenicity islands
16.3 Regulation and stability
16.4 Origin and acquisition of pathogenicity islands
16.5 Pai function in gram-negative and gram-positive pathogens
16.6 Pais in plant pathogens
16.7 Pai impacts on bacterial evolution
Acknowledgments
References
Chapter 17. Gene regulatory networks and hierarchies in bacterial pathogens
Abstract
17.1 The governance of gene expression
17.2 Coordination of gene expression
17.3 Gene control in networks and hierarchies: a regulatory architecture
17.4 Physical architecture of the genome—implications for gene control
17.5 Virulence gene regulation in Salmonella
17.6 The complex ToxR/ToxT regulon of Vibrio cholerae
17.7 Regulation of host cell invasion genes in Shigella flexneri
17.8 Conclusions
Acknowledgments
References
Part 4: Bacterial invasion
Chapter 18. Bacterial adhesion
Abstract
18.1 Introduction
18.2 Nonbacterial adhesins
18.3 Adhesins of gram-positive bacteria
18.4 Adhesins of gram-negative bacteria
18.5 Receptors of gram-negative adhesins
18.6 Antiadhesion strategies
18.7 Concluding remarks
References
Chapter 19. Invasion
Abstract
19.1 Salmonella
19.2 Invasion of other bacteria closely related to Salmonella
References
Chapter 20. Listeria monocytogenes cell-to-cell spread
Abstract
20.1 Introduction
20.2 Listeria monocytogenes diversity
20.3 Mechanisms of Listeria monocytogenes infection
20.4 Mechanisms of Listeria monocytogenes cell-to-cell spread
20.5 Conclusions
Acknowledgments
References
Chapter 21. Pattern recognition receptors and the innate immune network
Abstract
21.1 No reaction without recognition
21.2 Pattern recognition receptors
21.3 Membrane-bound pattern recognition receptors
21.4 Cytosolic pattern recognition receptors
21.5 Serum-associated pattern recognition receptors
21.6 From homeostasis to inflammation
21.7 Pattern recognition receptor evasion—now you see me, now you don’t
21.8 Conclusions
References
Chapter 22. Survival strategies of extracellular bacterial pathogens
Abstract
22.1 Introduction
22.2 The innate immune system
22.3 Defensive strategies for extracellular bacterial survival
22.4 Offensive strategies for extracellular bacterial survival
22.5 Conclusion
References
Chapter 23. Survival strategies of intracellular bacterial pathogens
Abstract
23.1 Introduction
23.2 Cell entry
23.3 Life in the vacuole
23.4 Life in the cytosol
23.5 Other survival strategies
23.6 Concluding remarks
Acknowledgments
References
Chapter 24. Viral–bacterial interactions within hosts
Abstract
24.1 Introduction
24.2 Scenario I: acute influenza–bacterial coinfection
24.3 Pathogenic mechanisms of influenza–bacterial coinfection
24.4 Conclusions of influenza–bacterial coinfection
24.5 Scenario II: the tuberculosis and human immunodeficiency virus syndemic
24.6 Clinical perspective of human immunodeficiency virus and Mtb coinfection
24.7 Pathogenic mechanisms of Mtb and human immunodeficiency virus coinfection
24.8 Conclusions of tuberculosis/human immunodeficiency virus coinfection
24.9 Overall conclusions
References
Part 5: Bacterial identification
Chapter 25. Molecular taxonomy
Abstract
25.1 Introduction
25.2 History of taxonomy
25.3 Bacterial species, type strains and nomenclature
25.4 “Candidatus” and the taxonomy of unculturable bacteria
25.5 Classification methods for prokaryotes
25.6 Methods for molecular taxonomy
25.7 The future of molecular taxonomy
References
Chapter 26. Bacterial whole-genome determination and applications
Abstract
26.1 Introduction
26.2 Bacterial genomes
26.3 Bacterial genome sequencing methods
26.4 Bacterial gene annotation
26.5 Bacterial genome submission to GenBank
26.6 Pan-genome analysis
26.7 Genome evolution and phylogenetic tree analysis
26.8 Prediction of subcellular localization and adhesin
26.9 Reverse vaccinology
26.10 Genome-based virulence factor prediction
26.11 Genome sequencing-based diagnosis
26.12 Genomic epidemiology
26.13 Microbiome and metagenomics
26.14 Challenges and opportunities
26.15 Concluding remarks
Acknowledgments
References
Chapter 27. Molecular detection of antimicrobial resistance
Abstract
27.1 General overview
27.2 Mechanism of detection of antimicrobial resistance
27.3 Mold
References
Chapter 28. Molecular epidemiology of antibiotic resistance in humans and animals
Abstract
28.1 Definitions
28.2 Processes of antibiotic resistance emergence and transmission
28.3 Genotyping methods for molecular epidemiology
28.4 Plasmid or bacterium: which is really responsible for the spread of resistance?
28.5 Origins of resistance genes
28.6 Epidemiology of antibiotic resistance in bacteria from farm animals
28.7 The role of wildlife in the spread of antibiotic resistance
28.8 Conclusions
References
Part 6: Bacterial control
Chapter 29. Mammalian antimicrobial peptides: defensins and cathelicidins
Abstract
29.1 Defensins
29.2 Cathelicidins
29.3 Conclusion
References
Chapter 30. Use of phages as antimicrobial agents
Abstract
30.1 Introduction
30.2 Phages as treatments
30.3 Phages as the source of antibacterials
30.4 Future perspectives
References
Chapter 31. Modes of action of antibacterial agents
Abstract
31.1 Inhibition of peptidoglycan biosynthesis
31.2 Cytoplasmic stages of peptidoglycan synthesis
31.3 Precursor translocation across the cytoplasmic membrane
31.4 Peptidoglycan assembly
31.5 Cross-linking of peptidoglycan
31.6 Mycolic acid and arabinogalactan synthesis in mycobacteria
31.7 The cytoplasmic membrane
31.8 Colistin
31.9 Daptomycin
31.10 Nucleic acid as a target for selective toxicity
31.11 Precursor synthesis
31.12 Chromosome organization
31.13 DNA replication
31.14 Transcription
31.15 Translation into protein
31.16 Folate antagonists
31.17 Sulfonamides
31.18 Dihydrofolate reductase inhibitors
31.19 Sulfonamide combinations
31.20 Antibiotics active against DNA architecture
31.21 Nitroimidazoles and nitrofurans
31.22 Inhibitors of DNA transcription
31.23 Inhibitors of translation in protein biosynthesis
31.24 Aminocyclitol (aminoglycoside) antibiotics
31.25 Tetracyclines
31.26 Chloramphenicol
31.27 Macrolide and azalide antibiotics
31.28 Oxazolidinones (linezolid and tedizolid phosphate)
31.29 Streptogramins
31.30 Clindamycin
31.31 Pleuromutilins (retapamulin, lefamulin)
31.32 Fusidic acid
31.33 Mupirocin
References
Chapter 32. Design of antibacterial agents
Abstract
32.1 Introduction
32.2 The “lead” compound or series of compounds
32.3 Drug profile
32.4 Choice and validation of the biochemical target
32.5 Selective toxicity
32.6 The desired antibacterial spectrum
32.7 Penetration to periplasmic and cytoplasmic biochemical target sites
32.8 Pharmacokinetics and bioavailability
32.9 Chemical design approaches
32.10 Case study: the design of antibacterial agents that inhibit DNA gyrase at the B-subunit
References
Chapter 33. Bacterial CRISPR systems and applications
Abstract
33.1 Introduction
33.2 A brief history of CRISPR
33.3 Functional divergence of CRISPR-Cas system
33.4 Structural basis of Cas9 and Cas12a nucleases
33.5 CRISPR-based genome editing in pathogenic bacteria
33.6 Sequence-specific antimicrobial agents
33.7 Transcriptional regulation by dCas tools
33.8 CRISPR-guided transposition
33.9 Base editing
33.10 Prime editing
References
VOLUME 2
Part 7: Disseminating bacterial infections
Chapter 34. Staphylococcus aureus
Abstract
34.1 Taxonomy
34.2 Epidemiology and transmission
34.3 Resistance to antibiotics
34.4 Genome
34.5 Factors that promote colonization and infection
34.6 Evasion of innate immune responses
34.7 Interfering with adaptive immunity
34.8 Colonization of the host
34.9 Regulation of expression of virulence factors
34.10 Persisters and small colony variants
34.11 Biofilm
34.12 Conclusions and future prospects
References
Chapter 35. Coagulase negative staphylococci
Abstract
35.1 Introduction
35.2 Staphylococcus epidermidis
35.3 Biofilm maturation
35.4 Staphylococcus lugdunensis
35.5 Secreted virulence factors
35.6 Interactions with professional phagocytes
35.7 Biofilm
35.8 Staphylococcus saprophiticus
35.9 Staphylococcus haemolyticus
35.10 Staphylococcus capitis
35.11 Conclusions and future prospects
References
Chapter 36. Streptococcus pyogenes
Abstract
36.1 Identification
36.2 Classification
36.3 Epidemiology
36.4 Physiology
36.5 The genetic architecture of the streptococcal virulence factors
36.6 Virulence factors and regulation
36.7 Pathogenesis
36.8 Pathogen–host interactions
36.9 Evasion of the adaptive immune response
36.10 Prevention and control of gas infection
36.11 Summary
Acknowledgments
References
Chapter 37. The enterococci
Abstract
37.1 History
37.2 Classification and identification
37.3 Environmental and gastrointestinal colonization
37.4 Pathogenicity
37.5 Molecular epidemiology
37.6 Clinical aspects of enterococcal infections
37.7 Antibiotic resistance
37.8 Conclusion
References
Chapter 38. Nocardia and Actinomyces
Abstract
38.1 Nocardia
38.2 Nocardia taxonomy
38.3 Metabolism and physiology of Nocardia
38.4 Proteins of pathogenic nocardias
38.5 Antibiotic-like metabolites of Nocardia
38.6 Diseases caused by Nocardia
38.7 Recognition and differentiation of Nocardia spp
38.8 Nucleic acid methodology
38.9 Molecular typing methods
38.10 Mass pectrometry (MALDI-TOF MS) methodology
38.11 Chemotherapy for nocardiosis
38.12 Experimental models for Nocardia pathogenicity
38.13 Mechanisms of Nocardia pathogenicity
38.14 Lung invasion
38.15 Brain invasion
38.16 Invasion of tissue culture cells
38.17 Nocardia genome
38.18 Actinomyces
Acknowledgments
References
Chapter 39. Pseudomonas aeruginosa
Abstract
39.1 Introduction
39.2 Pathogenesis
39.3 Quinolone-dependent quorum sensing system
39.4 Anti-Pseudomonas approaches
39.5 Concluding remarks
References
Chapter 40. Burkholderia pseudomallei and Burkholderia mallei
Abstract
40.1 The organisms
40.2 Associated diseases
40.3 Pathophysiology
40.4 Molecular biology of Burkholderia pseudomallei
40.5 Molecular biology of Burkholderia mallei
40.6 Mutation studies
40.7 Clinical laboratory tests
40.8 Primary culture and preliminary screening methods
40.9 Definitive identification
40.10 PCR-based identification
40.11 Genotyping
40.12 The future
40.13 Conclusions
Acknowledgment
References
Chapter 41. Acinetobacter baumannii
Abstract
41.1 Introduction
41.2 Transmission
41.3 Pathogenesis
41.4 Virulence factors
41.5 Integrated summary of current understanding of Acinetobacter baumannii pathogenesis
41.6 Antibiotic resistance drives outcomes
41.7 Clinical manifestations
41.8 Current treatment options
41.9 Combination antimicrobial therapy
41.10 Future treatment options
41.11 Conclusions
References
Part 8: Cutaneous and oral bacterial infections
Chapter 42. Cutibacterium (previously Propionibacterium) acnes and disease
Abstract
42.1 The genus Cutibacterium: a general overview
42.2 Cutibacterium acnes intraspecies diversity
42.3 Role of Cutibacterium acnes in human disease
42.4 Molecular mechanisms of pathogenesis
42.5 Molecular mechanisms of antimicrobial resistance
42.6 Genomics
42.7 Molecular characterization of Cutibacterium acnes
42.8 Conclusions
References
Chapter 43. Aggregatibacter
Abstract
43.1 Microbiology
43.2 Virulence factors
43.3 Molecular detection
43.4 Clinical relevance
43.5 Conclusions
References
Chapter 44. Dental caries
Abstract
44.1 Structure of teeth
44.2 Types of dental caries
44.3 Caries in populations
44.4 Important microorgansms in caries
44.5 Virulence mechanisms of Streptococcus mutans
44.6 Host factors in caries
44.7 Antimicrobial strategies in caries
References
Part 9: Gastrointestinal bacterial infections: toxin associated
Chapter 45. Clostridium botulinum and associated neurotoxins
Abstract
45.1 Introduction
45.2 The bacterium: Clostridium botulinum
45.3 The toxins: botulinum neurotoxins
45.4 The disease: botulism
45.5 Conclusions
References
Chapter 46. Clostridioides difficile: from “difficult to grow” to “difficult to treat”
Abstract
46.1 Introduction and historical perspective
46.2 Epidemiology
46.3 Pathophysiology
46.4 Virulence determinants
References
Chapter 47. The Bacillus cereus group
Abstract
47.1 Taxonomy
47.2 Commonly used genomic and typing approaches
47.3 Isolation and identification
47.4 Emetic food poisoning
47.5 Assays for emetic toxins
47.6 Nongastrointestinal infections
47.7 Local infections
47.8 Systemic infections
47.9 Virulence factors of Bacillus cereus
47.10 Emetic toxin
47.11 Cereulide structure, biosynthesis, and regulation
47.12 Activities and mechanisms
47.13 Nonemetic toxicity in vivo
47.14 Hemolysin BL family of tripartite toxins
47.15 Genetic organization
47.16 Distribution and prevalence
47.17 Biological activities
47.18 Structure
47.19 Mechanism of pore formation
47.20 Haemolysin BL and nonhemolytic enterotoxin in virulence
47.21 Hemolysins
47.22 Cereolysin O in virulence
47.23 Hemolysin II
47.24 Hemolysin II in virulence
47.25 Regulation of expression of the hlyII gene
47.26 Haemolysin III
47.27 Cytotoxin K (haemolysin IV)
47.28 Hemolysin IV (cytotoxin K) and virulence
47.29 Phospholipases
47.30 Sphingomyelinase
47.31 Phosphatidylcholine-preferring phospholipase C
47.32 Phosphatidylinositol phospholipase C
47.33 Phospholipases and virulence
47.34 Proteases and peptidases
47.35 CwpFM (EntFM)
47.36 Siderophores and iron acquisition
47.37 Pleiotropic regulation of virulence factors
47.38 Conclusions
References
Chapter 48. Vibrio cholerae
Abstract
48.1 Introduction
48.2 History
48.3 Nomenclature and classification
48.4 Genome
48.5 Epidemiology
48.6 Clinical manifestations and pathogenesis
48.7 Diagnosis
48.8 Treatment
48.9 Prevention
48.10 Conclusion
References
Chapter 49. Aeromonas
Abstract
49.1 Introduction
49.2 History
49.3 Classification
49.4 Morphology and structure
49.5 Genome organization
49.6 Biochemical characteristics
49.7 Biology and epidemiology
49.8 Clinical features
49.9 Pathogenesis
49.10 Identification and diagnosis
49.11 Treatment and prevention
49.12 Future perspectives
References
Chapter 50. Plesiomonas
Abstract
50.1 Introduction
50.2 Morphology and phenotypic characteristics
50.3 Cultivation, identification, and serotyping
50.4 Habitat and ecology
50.5 Clinical features
50.6 Conclusions
References
Part 10: Gastrointestinal bacterial infections: superficial
Chapter 51. Diarrheagenic Shigella
Abstract
51.1 Classification
51.2 Description of the genus
51.3 Pathogenesis
51.4 Epidemiology and transmission
51.5 Clinical significance
51.6 Collection, transportation, and storage of specimens
51.7 Direct detection
51.8 Separation procedures
51.9 Identification
51.10 Typing system
51.11 Serological tests
51.12 Sensitivity to antimicrobial drugs
51.13 Evaluation, interpretation, and reporting of the results
References
Chapter 52. Vibrio parahaemolyticus and Vibrio vulnificus
Abstract
52.1 Vibrio parahaemolyticus
52.2 Vibrio vulnificus
References
Chapter 53. Pathogenic Escherichia coli
Abstract
53.1 Basic biology
53.2 Intraintestinal pathogenic Escherichia coli
53.3 Extraintestinal pathogenic Escherichia coli
53.4 Conclusion
Acknowledgment
References
Chapter 54. Campylobacter
Abstract
54.1 Introduction
54.2 The genome
54.3 Conclusions
Acknowledgments
References
Chapter 55. Helicobacter pylori
Abstract
55.1 Structure and morphology
55.2 Isolation, identification, and preservation
55.3 Pathology and pathogenicity
55.4 Diagnosis
55.5 Epidemiology and transmission
55.6 Therapy
55.7 Genome
55.8 Proteome
55.9 Major characterized proteins
55.10 Virulence mechanisms
55.11 Conclusions
References
Chapter 56. Tropheryma whipplei
Abstract
56.1 Introduction
56.2 Classification
56.3 Morphology
56.4 Genome
56.5 Biology and epidemiology
56.6 Clinical features
56.7 Pathogenesis
56.8 Diagnosis
56.9 Treatment
56.10 Conclusion
References
Part 11: Gastrointestinal bacterial infections: systemic
Chapter 57. Salmonella Typhi and Salmonella Paratyphi
Abstract
57.1 Introduction
57.2 Classification and nomenclature
57.3 Diagnosis of typhoid and paratyphoid fever
57.4 Analysis of Salmonella genome
57.5 Genetic variability within serovars: strain typing
57.6 Host restriction
57.7 Infection process
57.8 Cell and animal models
57.9 Carrier state
57.10 Invasive nontyphoidal Salmonella
57.11 Antimicrobial control of typhoid fever
57.12 Vaccines
57.13 Conclusions
References
Chapter 58. Interactions of nontyphoidal Salmonella with host cells
Abstract
58.1 Introduction
58.2 Invasion of epithelial cells and intestinal mucosa
58.3 Intracellular survival and tissue dissemination
58.4 Induction of host cell death
58.5 Indirect interactions with host cells in the inflamed intestine
58.6 Immune evasion
58.7 Concluding remarks
Acknowledgments
References
Chapter 59. Yersinia enterocolitica
Abstract
59.1 Introduction
59.2 Taxonomy and phylogeny
59.3 Genomics
59.4 Epidemiology and control
59.5 Pathogenesis
59.6 Clinical manifestations
59.7 Diagnosis
59.8 Antimicrobial treatment
59.9 Conclusions
References
Chapter 60. Listeria monocytogenes
Abstract
60.1 Introduction
60.2 Listeria monocytogenes physical characteristics and distribution
60.3 Clinical manifestations of infection
60.4 Pathogenesis
60.5 Host cell invasion
60.6 Listeria monocytogenes escape from host cell vacuoles
60.7 Cytosolic bacterial replication and cell-to-cell spread
60.8 Regulation of Listeria monocytogenes virulence
60.9 Host immune responses to Listeria monocytogenes infections
60.10 Concluding remarks
References
Part 12: Urogenital bacterial infections
Chapter 61. Uropathogenic Escherichia coli in urinary tract infections
Abstract
61.1 Introduction
61.2 Epithelial adhesion and pili
61.3 Toxins
61.4 Other virulence determinants
61.5 Invasion of uropathogenic Escherichia coli into the uroepithelium
61.6 Intracellular lifestyles of uropathogenic Escherichia coli during cystitis
61.7 Models for complicated urinary tract infections
61.8 Immune response and evasion
61.9 Host susceptibility determinants
61.10 Antimicrobial resistance and antivirulence strategies
61.11 Vaccine prospects
61.12 Conclusion
Acknowledgment
References
Chapter 62. Urinary tract infections caused by Proteus mirabilis
Abstract
62.1 Proteus mirabilis: a model of a non-Escherichia coli urinary pathogen
62.2 Common themes in pathogenicity
62.3 Motility
62.4 Reciprocal regulation of fimbriae and flagella
62.5 Swarming and intermicrobial interactions
62.6 Crystalline biofilm formation
62.7 Nutrition acquisition that impacts infection
62.8 Metal acquisition
62.9 Toxins
62.10 Urease, pH, and nitrogen metabolism
62.11 Lipopolysaccharide
62.12 Evasion of the host response
62.13 Horizontal gene transfer
62.14 Antimicrobial resistance
62.15 Vaccine development
62.16 Recent findings
62.17 Conclusion
Acknowledgment
References
Chapter 63. Uncultivable pathogenic treponemes
Abstract
63.1 Introduction
63.2 Classification
63.3 Clinical symptoms of treponemal infections
63.4 Treponeme structure and physiology, genomic insights into treponemal metabolism
63.5 Genetic and genomic analyses
63.6 Pathogenesis of treponemal infections
63.7 Host susceptibility and treponemal immunology
63.8 Diagnosis and therapy
63.9 Epidemiology, control, and prevention
63.10 Evolution of pathogenic treponemes and the origin of syphilis
Acknowledgments
References
Chapter 64. Haemophilus ducreyi: chancroid
Abstract
64.1 Epidemiology
64.2 Physiology
64.3 Host response to infection
64.4 Determinants of pathogenicity
64.5 Clinical infection and disease
64.6 Diagnosis
64.7 Antimicrobial treatment and prevention
References
Chapter 65. Chlamydia trachomatis
Abstract
65.1 Introduction
65.2 Clinical significance, epidemiology, and transmission
65.3 C. trachomatis persistence
65.4 Effects on cell division and death: inhibition of apoptosis
65.5 Virulence factors
65.6 C. trachomatis chromosomes
65.7 Vaccine development
65.8 Sampling, sample storage, and transportation
65.9 Diagnosis of chlamydial infections
65.10 Evaluation, interpretation, and reporting of results
65.11 Treatment
65.12 Summary and recommendations
65.13 Concluding remarks
References
Chapter 66. Neisseria gonorrhoeae
Abstract
66.1 Introduction
66.2 Classification
66.3 Genetics
66.4 Clinical manifestations of disease
66.5 Coinfection
66.6 Pathogenesis
66.7 Host immunity to gonococcal infection
66.8 Immune evasion
66.9 Diagnosis
66.10 Antimicrobial therapy and resistance
66.11 New treatment
66.12 Gonococcal vaccine
References
Chapter 67. Bacterial vaginosis and associated bacteria
Abstract
67.1 Microbiology
67.2 Diagnosis
67.3 Treatment
67.4 Controversies
References
VOLUME 3
Part 13: Central nervous system bacterial infections
Chapter 68. Haemophilus influenzae
Abstract
68.1 Introduction to Haemophilus influenzae
68.2 Diseases caused by Haemophilus influenzae
68.3 Haemophilus influenzae, carriage, disease transmission, and treatment
68.4 Haemophilus influenzae epidemiology
68.5 Laboratory identification of Haemophilus influenzae
68.6 Genetic diversity of Haemophilus influenzae
68.7 Role of virulence factors in pathogenesis of Haemophilus influenzae
68.8 Antimicrobial resistance
68.9 Reduced susceptibility to β-lactam antimicrobial agents in Haemophilus influenzae
68.10 Reduced susceptibility to rifamycin used for chemoprophylaxis
68.11 Resistance to other antimicrobics
68.12 The risk of emerging Haemophilus influenzae antimicrobial resistance
68.13 Conclusion and future perspectives
References
Chapter 69. Neisseria meningitidis
Abstract
69.1 Overview of the meningococcus
69.2 Progression of meningococcal disease
69.3 Molecular virulence determinants
69.4 Diagnosis and management of meningococcal disease
69.5 Vaccination
69.6 Conclusions
Acknowledgments
References
Chapter 70. Streptococcus agalactiae (Group B Streptococcus)
Abstract
70.1 Introduction
70.2 Clinical presentations and epidemiology
70.3 Diagnosis and treatment
70.4 Pathogenesis
70.5 Vaccination
References
Part 14: Respiratory bacterial infections
Chapter 71. Bordetella pertussis
Abstract
71.1 Bordetella pertussis
71.2 The Bordetella genus
71.3 The evolution of Bordetella pertussis
71.4 Epidemiology and resurgence of pertussis disease
71.5 Clinical disease manifestations and treatment of Bordetella pertussis infection
71.6 Bacterial characteristics and microbiology of Bordetella pertussis
71.7 Virulence factors and host pathogen interactions
71.8 B. pertussis evolution and variation in the vaccine era
71.9 Current and future prevention of B. pertussis infection
References
Chapter 72. Streptococcus pneumoniae
Abstract
72.1 Introduction
72.2 Streptococcus pneumoniae identification
72.3 Pneumococcal capsular polysaccharides and serotypes
72.4 Antimicrobial resistance
72.5 Pneumococcal clones
72.6 Colonization, transmission, and invasion
72.7 Pneumococcal vaccines
References
Chapter 73. Know your enemy: Klebsiella pneumoniae
Abstract
73.1 Introduction
73.2 Epidemiology and regional outbreaks
73.3 Pathogenesis
73.4 Colonization and systemic infection
73.5 Antimicrobial resistance
73.6 Host–pathogen interaction
73.7 Novel therapeutics and vaccines
73.8 Concluding remarks
References
Chapter 74. Moraxella catarrhalis
Abstract
74.1 Introduction
74.2 History and taxonomy
74.3 Morphology and biochemical characteristics
74.4 Genome organization and functions
74.5 Pathogenic mechanisms
Acknowledgment
References
Chapter 75. Mycoplasmas and ureaplasmas
Abstract
75.1 Classification
75.2 Identification
75.3 Structure
75.4 Cell biology and pathogenesis
75.5 Methods for detection and characterization
75.6 Molecular typing systems and organism subtypes
75.7 Antimicrobial resistance
References
Chapter 76. Legionella
Abstract
76.1 Introduction
76.2 Taxonomy, morphology, and genome
76.3 Biology and epidemiology
76.4 Clinical features
76.5 Pathogenesis
76.6 Identification and diagnosis
76.7 Treatment and prevention
76.8 Conclusions
References
Chapter 77. Nondiphtheriae Corynebacterium spp. as emerging respiratory pathogens
Abstract
77.1 A review of Corynebacterium diphtheriae
77.2 Nondiphtheriae Corynebacterium spp. as emerging respiratory pathogens
77.3 MALDI-TOF Ms
77.4 Conclusion
References
Part 15: Mycobacterial infections
Chapter 78. Mycobacterium tuberculosis
Abstract
78.1 The great white plague
78.2 Global epidemiology
78.3 The contagious nature of tuberculosis
78.4 Basic microbiology
78.5 Relevant pathophysiology
78.6 Immunity
78.7 Tuberculosis comorbidities
78.8 Molecular epidemiology and DNA fingerprinting
78.9 Diagnosis of latent tuberculosis infection
78.10 Treatment of latent tuberculosis infection
78.11 Diagnosis of active tuberculosis
78.12 Antimicrobial therapy
78.13 Vaccines
References
Chapter 79. Mycobacterium leprae and beyond
Abstract
79.1 The disease
79.2 The pathogen
79.3 Host response
79.4 Prevention of leprosy
References
Chapter 80. The Mycobacterium avium complex and slowly growing mycobacteria
Abstract
80.1 Diseases of nontuberculous mycobacteria
80.2 Nontuberculous mycobacteria pulmonary disease
80.3 Nontuberculous mycobacteria sinusitis and otitis media
80.4 Mycobacterial cervical lymphadenitis in children
80.5 Bacteremia in immunodeficient or immunosuppressed individuals
80.6 Device and hospital-acquired infections
80.7 Differential diagnosis of nontuberculous mycobacteria infection
80.8 Physiologic and structural features relevant to nontuberculous mycobacteria epidemiology
80.9 Nontuberculous mycobacteria adaptation
80.10 Geospatial distribution of nontuberculous mycobacteria disease
80.11 Environmental sources of nontuberculous mycobacteria
80.12 Inhibition of nontuberculous mycobacteria adherence and biofilm formation by Methylobacterium spp
80.13 Comment on routine surveying for Mycobacterium spp. in premise plumbing
80.14 Methods to reduce human nontuberculous mycobacteria exposure
80.15 Laboratory diagnosis of nontuberculous mycobacteria infection
80.16 Treatment and measurement of antibiotic susceptibility of nontuberculous mycobacteria isolates
80.17 Unique features of the Mycobacterium avium complex
References
Chapter 81. Rapidly growing mycobacteria
Abstract
81.1 Introduction
81.2 Molecular methods for identification of rapidly growing mycobacteria
81.3 Genotyping of rapidly growing mycobacteria
References
Part 16: Zoonotic bacterial infections
Chapter 82. Pasteurella
Abstract
82.1 Introduction
82.2 Phenotypic characteristics of Pasteurella sensu stricto
82.3 Separation of species of the genus Pasteurella
82.4 Description of the species of Pasteurella
82.5 Maintenance procedures
82.6 Isolation procedures
82.7 Chemotaxonomic properties
82.8 Cell wall
82.9 Nutrition and growth conditions
82.10 Genomics
82.11 Plasmids, integrated conjugative elements, and bacteriophages
82.12 Virulence factors
82.13 Antibiotic sensitivity
82.14 Ecology and habitat
82.15 Misclassified species
82.16 Reclassified and unnamed species
References
Chapter 83. Brucella
Abstract
83.1 Brucella genus and species
83.2 Bacteriology
83.3 Epidemiology and transmission to humans
83.4 Bacterial structure and main molecules
83.5 Brucella intracellular life cycle
83.6 General clinical picture of human brucellosis
83.7 Immune response
83.8 Immune escape mechanisms
83.9 Pathogenesis and immunopathogenesis
83.10 Laboratory diagnosis
83.11 Antimicrobial therapy for human brucellosis
83.12 Conclusion
References
Chapter 84. Bacillus anthracis and other Bacillus species
Abstract
84.1 Bacillus species similarities and differences
84.2 Medical and public health importance
84.3 Bacillus anthracis pathogenesis
84.4 Sporulation and germination
84.5 Virulence factors
84.6 Basic identification and diagnosis of Bacillus species
84.7 Vaccines
84.8 Animal models for anthrax
References
Chapter 85. Yersinia pestis
Abstract
85.1 Introduction
85.2 Isolation and taxonomy of Yersinia pestis
85.3 Evolution of Yersinia pestis: from sequence to function
85.4 Physiology of Yersinia pestis
85.5 Immunity and pathogenicity of Yersinia pestis
85.6 Conclusions
References
Chapter 86. Borrelia burgdorferi and other Borrelia species
Abstract
86.1 Taxonomy
86.2 Identification
86.3 Morphology
86.4 Physiology
86.5 Genome
86.6 Population genetics
86.7 Pathogenesis
86.8 Immunity
86.9 Diagnosis
86.10 Antimicrobial therapy
86.11 Epidemiology and control
Acknowledgments
References
Chapter 87. Coxiella and Q fever
Abstract
87.1 Introduction
87.2 Classification
87.3 Morphology
87.4 Physiology
87.5 Epidemiology
87.6 Transmission
87.7 Genetics
87.8 Immunology
87.9 Pathogenesis
87.10 Clinical signs and symptoms
87.11 Identification and diagnosis
87.12 Treatment
87.13 Prevention and surveillance
87.14 Conclusions
References
Chapter 88. Leptospira and leptospirosis
Abstract
88.1 Historical aspects
88.2 Transmission cycle
88.3 Epidemiology
88.4 Classification
88.5 Leptospira microbiology
88.6 Growth conditions
88.7 Genome
88.8 Virulence factors
88.9 Clinical manifestations
88.10 Diagnostic methods
88.11 Treatment
88.12 Prevention and control
88.13 Leptospira immunity
88.14 Immune evasion in leptospirosis
88.15 Conclusion
References
Chapter 89. Anaplasma
Abstract
89.1 Introduction
89.2 History and phylogenetics
89.3 Eco-epidemiology
89.4 Human granulocytic anaplasmosis clinical features, diagnosis, and treatment
89.5 Microbial colonization and pathogenesis
89.6 Colonization of the tick vector
89.7 Immunology and immunobiology of human granulocytic anaplasmosis
89.8 Vaccination against Anaplasma phagocytophilum
89.9 Conclusion and future directions
89.10 Summary
References
Chapter 90. Francisella tularensis
Abstract
90.1 Introduction
90.2 Taxonomy, epidemiology, and ecology
90.3 Tularemia symptoms
90.4 Diagnosis and detection
90.5 Therapy
90.6 Intracellular life cycle and pathogenesis
90.7 Vaccine development
90.8 Summary
References
Part 17: Novel approaches for bacterial infections
Chapter 91. Genomic analysis of microbial infections
Abstract
91.1 Introduction
91.2 Nucleic acid probe hybridization
91.3 Nucleic acid amplification
91.4 Target amplification
91.5 Molecular typing
91.6 Microarrays
91.7 Nucleic acid sequencing
91.8 Next-generation sequencing
91.9 Current challenges and considerations for molecular diagnostic methods in clinical practice
91.10 Expressed sequences are not necessarily expressed
References
Chapter 92. Omic approaches to infectious disease testing
Abstract
92.1 Introduction
92.2 Current host response biomarkers for infection
92.3 Methods in transcriptomics
92.4 Methods in proteomics/metabolomics
92.5 Diseases and syndromes
References
Chapter 93. Proteomic analysis of microbial infections
Abstract
93.1 Introduction
93.2 Common mass spectrometry platforms and general setups in the applications of microbial infections
93.3 Proteomics applications in microbial identification and typing
93.4 Mass spectrometry applications in antimicrobial resistance study and susceptibility tests
93.5 Proteomics applications on microbe–cell and microbe–host interactions
93.6 Conclusions and future perspectives
References
Further reading
Chapter 94. Analysis of microbial infections with omic techniques
Abstract
94.1 “Omic” technologies: concept and development
94.2 Genomics and genomic analysis
94.3 Transcriptomics and transcriptomic techniques
94.4 Proteomics and proteomic techniques
94.5 Metabolomics and metabonomic techniques
94.6 Concluding remarks
References
Chapter 95. Bioinformatics in the study of microbial infections
Abstract
95.1 Bioinformatics in the study of microbial infections
95.2 Tools for bioinformatics analysis
95.3 Bioinformatics analysis of genome sequences for epidemiology
95.4 Bioinformatics to interrogate metagenomes
95.5 Summary
References
Chapter 96. The human microbiota and its therapeutic options
Abstract
96.1 Introduction
96.2 Overview of human microbiota
96.3 Methods to study human microbiota
96.4 Human microbiota of different sites
96.5 Human microbiota and disease
96.6 Microbiota-based therapeutic options
96.7 Conclusions
Acknowledgment
References
Chapter 97. Biomarkers of sepsis
Abstract
97.1 Introduction
97.2 Description of biomarkers
97.3 Clinical significance of sepsis biomarkers
97.4 Conclusion
References
Chapter 98. Reverse vaccinology
Abstract
98.1 Brief history of vaccinology
98.2 Reverse vaccinology
98.3 Refinements to reverse vaccinology (as applied to Neisseria meningitidis)
98.4 Application of reverse vaccinology to other pathogens
98.5 Related high-throughput approaches
98.6 Conclusion
References
Chapter 99. CRISPR/Cas-based diagnosis and treatment of infectious diseases
Abstract
99.1 Introduction
99.2 CRISPR-based detection of infectious viruses
99.3 Detection based on collateral cleavage: other Cas proteins
99.4 The strengths of CRISPR/Cas-based pathogen detection systems
99.5 The applications of the CRISPR/Cas systems in antiviral therapy
99.6 Outlook and future directions
99.7 Next-generation CRISPR-based infectious diagnostic
99.8 CRISPR-based efficient and safe antiviral therapy
Acknowledgments
Abbreviations
References
VOLUME 4
Part 18: Viral structure and function
Chapter 100. Classification of medically important viruses
Abstract
100.1 Introduction
100.2 RNA viruses
100.3 DNA viruses
100.4 Unusual viral agents
100.5 Future perspectives
References
Chapter 101. An introduction to principles of virus structure
Abstract
101.1 Brief history of structural virology
101.2 Structural classification of viruses
101.3 Structures of viral proteins
101.4 Alphavirus capsid protein
101.5 Coronavirus spike protein
Acknowledgments
References
Chapter 102. Enterovirus entry and uncoating
Abstract
102.1 Enteroviruses – general knowledge
102.2 Enterovirus stability and structure outside cells
102.3 Receptor binding
102.4 Cell entry
102.5 Enterovirus uncoating
102.6 What is known about the actual genome release?
References
Chapter 103. RNA virus replication
Abstract
103.1 Replication and gene expression of RNA viruses
103.2 Viral replication compartments
References
Chapter 104. DNA virus replication
Abstract
104.1 Viral genome classification, organization, and topology
104.2 Replication and gene expression of DNA viruses
104.3 Viral replication compartments
References
Chapter 105. Virus assembly
Abstract
105.1 Introduction
105.2 General organization of virions
105.3 Viral capsid and envelope proteins
105.4 General mechanisms of virus assembly
105.5 Assembly of icosahedral viruses
105.6 Structure and assembly of helical capsids
105.7 Structure and assembly of pleomorphic viruses
105.8 Summary
Funding
References
Chapter 106. Virus evolution
Abstract
106.1 Introduction
106.2 Hypothetic origins of viruses
106.3 Mutations underlying virus evolution
106.4 Key contributors to virus evolution
106.5 Impact of virus evolution
106.6 Conclusions
References
Chapter 107. Pathogenesis of viral infection
Abstract
107.1 Introduction of pathogenesis of viral infection
107.2 Definitions and concepts of viral pathogenesis
107.3 Viral determinants for pathogenesis
107.4 Host determinants for viral pathogenesis
107.5 Conclusions and outlooks
Acknowledgments
References
Chapter 108. Viruses, cell transformation, and cancer
Abstract
108.1 Introduction
108.2 Major viruses responsible for cellular transformation
108.3 Characteristics of cellular transformation
108.4 Cellular transformation and cancer development
108.5 Molecular mechanism of cellular transformation by viruses
108.6 Conclusion
References
Part 19: Bloodborne viral infections
Chapter 109. Human immunodeficiency virus
Abstract
109.1 Historical perspectives
109.2 Classification, origin, and genomic structure
109.3 Virion structure
109.4 Replication cycle
109.5 Epidemiology of the HIV pandemic
109.6 Clinical features and diagnostic evaluation
109.7 Antiretroviral therapy
109.8 Prevention
109.9 Future perspectives
References
Chapter 110. Hepatitis C virus
Abstract
110.1 Introduction
110.2 Etiology
110.3 HCV life cycle
110.4 Immunity and pathogenesis
110.5 Clinical manifestations
110.6 Diagnostic
110.7 Screening
110.8 Treatment
110.9 Vaccine
110.10 Conclusion
References
Chapter 111. Hepatitis B and Hepatitis D Viruses
Abstract
111.1 Hepatitis B Virus
111.2 Hepadnaviridae family
111.3 Particle morphology and properties
111.4 Genome organization and RNA transcripts
111.5 Viral proteins
111.6 Viral life cycle
111.7 Clinical features and pathogenesis
111.8 Detection and diagnosis
111.9 Hepatocellular carcinoma
111.10 Epidemiology
111.11 Therapies for management
111.12 Prevention
111.13 Hepatitis D Virus
111.14 Genome and virion properties
111.15 Life cycle
111.16 Co-infection versus superinfection
111.17 Clinical features and pathogenesis
111.18 Detection and diagnosis
111.19 Epidemiology
111.20 Hepatocellular carcinoma
111.21 Therapies for management
111.22 Prevention
References
Chapter 112. Ebola and Marburg viruses
Abstract
112.1 Introduction
112.2 History and taxonomy of Filoviridae
112.3 Natural history of filoviruses
112.4 Epidemiology
112.5 Basic virology
112.6 Pathogenesis
112.7 Diagnosis
112.8 Acute disease
112.9 Filovirus persistence in survivors
112.10 Clinical sequelae associated with filovirus disease
112.11 Patient care
112.12 Management of clinical sequelae
112.13 Therapeutics
112.14 Vaccine approaches against filoviruses
112.15 Disease control and outbreak management
112.16 Outlook
Acknowledgments
References
Part 20: Gastrointestinal viral infections
Chapter 113. Viral hepatitis A and E
Abstract
113.1 Introduction
113.2 History
113.3 Classification and genotypes
113.4 Epidemiology
113.5 Clinical features
113.6 Virion morphology and properties
113.7 Genome structure and viral proteins
113.8 Infectious life cycle
113.9 Immune responses and pathogenesis
113.10 Diagnosis
113.11 Treatment and prevention
113.12 Concluding remarks
References
Chapter 114. Rotavirus
Abstract
114.1 The etiologic agent—rotavirus
114.2 Classification of rotavirus
114.3 Pathogenesis
114.4 Clinical manifestation
114.5 Diagnosis
114.6 Treatment
114.7 Epidemiology
114.8 Rotavirus vaccines
114.9 Future rotavirus vaccines
References
Chapter 115. Gastroenteritis viruses other than rotaviruses
Abstract
115.1 Viruses and taxonomy
115.2 Disease burden, epidemiology, and transmission
115.3 Clinical significance
115.4 Laboratory diagnosis
115.5 Treatment, infection control, and prevention
References
Part 21: Respiratory viral infections
Chapter 116. Influenza viruses
Abstract
116.1 Historical perspectives
116.2 Classification and genomic structure
116.3 Virion structure
116.4 Replication cycle
116.5 Epidemiology of seasonal influenza
116.6 Clinical features and pathogenesis
116.7 Diagnostic testing
116.8 Antiviral therapy and chemoprophylaxis
116.9 Chemoprophylaxis
116.10 Influenza vaccines
116.11 Live attenuated influenza vaccines
116.12 Future perspectives: the need for a universal influenza vaccine
References
Chapter 117. Avian and swine influenza viruses
Abstract
117.1 Introduction
117.2 Influenza classification and structure
117.3 Pandemic influenza viruses
117.4 Zoonosis
117.5 Transmission
117.6 Epidemiology and clinical presentation
117.7 Pathogenesis
117.8 Prevention and control
117.9 Conclusions
References
Chapter 118. Adenoviruses
Abstract
118.1 Adenovirus classification
118.2 Adenovirus structure and replication
118.3 Adenovirus major receptors
118.4 Clinical features
118.5 Epidemiology
118.6 Anti-adenovirus drugs
118.7 Vaccines and vectors
References
Chapter 119. Respiratory syncytial virus and metapneumovirus
Abstract
119.1 Respiratory syncytial virus
119.1.2 Pathogenesis
119.1.3 Clinical characteristics
119.1.4 Treatment and prevention
119.1.5 Diagnosis
119.1.6 Epidemiology and transmission
119.1.7 Vaccines
119.2 Human metapneumovirus
119.2.2 Pathogenesis and clinical characteristics
119.2.3 Treatment and prevention
119.2.4 Diagnosis
119.2.5 Epidemiology and transmission
119.2.6 Vaccines
References
Chapter 120. Enteroviruses and rhinoviruses
Abstract
120.1 Introduction
120.2 Taxonomy
120.3 Virion structure and life cycle
120.4 Genomic characteristics
120.5 Epidemiology
120.6 Pathogenesis
120.7 Clinical diseases
120.8 Laboratory diagnosis
120.9 Treatment and prevention
References
Part 22: Insect-borne viral infections
Chapter 121. Hemorrhagic fever viruses
Abstract
121.1 Overview
121.2 Arenaviridae
121.3 Hantaviridae
121.4 Phenuiviridae
121.5 Nairoviridae
121.6 Flaviviridae
121.7 Filoviridae
121.8 Diagnosis and treatment
121.9 Prevention
121.10 Vaccines for viral hemorrhagic fevers
References
Chapter 122. Bunyavirales
Abstract
122.1 Introduction
122.2 Bunyavirales replication cycle
122.3 Bunyavirales human pathogens
122.4 Bunyavirales vaccines and antivirals
122.5 Laboratory diagnosis Bunyavirales
122.6 Bunyavirales transmission control
References
Chapter 123. Flaviviruses including Zika virus
Abstract
123.1 Introduction
123.2 Flaviviruses structure and morphogenesis
123.3 Flaviviruses virion assembly and maturation
123.4 Flaviviruses genome
123.5 Flaviviruses attachment and entry
123.6 Flaviviruses replication
123.7 Human antibody response against Flaviviruses infections
123.8 The Flaviviruses species
123.9 Flaviviruses laboratory diagnosis
123.10 Prevention of Flavivirus infection
123.11 Flavivirus vaccines
123.12 Flaviviruses treatment
References
Chapter 124. Viral encephalitis
Abstract
124.1 Introduction
124.2 Clinical features of viral encephalitis
124.3 Diagnosis of viral encephalitis
124.4 Specific causes of viral encephalitis
124.5 Conclusions
References
Part 23: Localized viral infections
Chapter 125. Human papillomaviruses
Abstract
125.1 Introduction
125.2 Classification, morphology, and genome
125.3 Biology and epidemiology
125.4 Clinical features
125.5 Pathogenesis
125.6 Identification and diagnosis
125.7 Treatment and prevention
125.8 Conclusions
References
Chapter 126. Herpes simplex viruses
Abstract
126.1 History
126.2 Epidemiology
126.3 Virology
126.4 Pathophysiology and pathogenesis
126.5 Immunity
126.6 Pathology
126.7 Clinical syndromes
126.8 Laboratory diagnosis
126.9 Treatment
126.10 Vaccine efforts
126.11 Herpes B virus
References
Chapter 127. Prions
Abstract
127.1 Prion diseases and prions
127.2 Prion protein structure
127.3 PrPC is essential for prion replication
127.4 Molecular basis of prion strains
127.5 Strain diversity in human prion diseases
127.6 Species barrier, prion strains transmission, selection, and adaptation
127.7 Synthetic prion strains
127.8 Diagnosis of prion diseases
127.9 Description of protein misfolded cyclic amplification
127.10 Protein misfolded cyclic amplification in prion research
127.11 Protein misfolded cyclic amplification in prion diseases diagnosis
127.12 Description of real-time quaking-induced conversion
127.13 Real-time quaking-induced conversion in prion research
127.14 Real-time quaking-induced conversion in prion diseases diagnosis
127.15 Treatment of prion diseases
127.16 Conclusions
References
Part 24: Viral diagnosis, control, and application
Chapter 128. Principles of diagnostic virology and virus discovery
Abstract
128.1 Introduction
128.2 Antigen detection
128.3 Viral culture
128.4 Serologic diagnosis
128.5 Nucleic acid detection
128.6 Amplification-based detection
128.7 Polymerase chain reaction and quantitative polymerase chain reaction
128.8 Multiplex polymerase chain reaction
128.9 Nucleic acid sequencing
128.10 Amplicon sequencing
128.11 Metagenomic sequencing
128.12 Outbreak investigation
128.13 Novel viral diagnosis
128.14 Summary
References
Chapter 129. Viral monitoring in immunocompromised hosts
Abstract
129.1 Introduction
129.2 Cytomegalovirus
129.3 Epstein–Barr virus
129.4 Hepatitis B virus
129.5 BK virus
129.6 Adenovirus
129.7 Human herpesvirus 6
129.8 Hepatitis C, human immunodeficiency virus, and increased risk donor solid organ transplant
References
Chapter 130. Molecular epidemiology of viral infections
Abstract
130.1 Introduction
130.2 Genetic diversity
130.3 Zoonotic origins of human viruses
130.4 Virus transmission
130.5 Viral pathogenesis
130.6 Concluding remarks: SARS-CoV-2
Acknowledgments
Reference
Chapter 131. Human virome in health and disease
Abstract
131.1 Introduction
131.2 The current achievements of human virome studies
131.3 Phage-derived applications
131.4 Phage interaction with the human immune system and implications of future pharmacy study
131.5 Conclusions
References
Chapter 132. Viral vectors for gene therapy
Abstract
132.1 What is gene therapy?
132.2 Non-adeno-associated virus viral vectors for gene therapy
132.3 Adeno-associated virus vectors: from discovery to commercialization
132.4 Current adeno-associated virus–based clinical trials
132.5 Manufacturing of recombinant adeno-associated virus vectors
132.6 Future perspectives
References
VOLUME 5
Part 25: COVID-19
Chapter 133. COVID-19: etiology
Abstract
133.1 Introduction
133.2 Coronaviruses
133.3 Severe acute respiratory syndrome coronavirus 2
133.4 Future perspectives
References
Chapter 134. COVID-19 therapy directed against pathogenic mechanisms of severe acute respiratory syndrome coronavirus 2
Abstract
Executive summary
134.1 Introduction
134.2 Pathogenic mechanisms of severe acute respiratory syndrome coronavirus 2
134.3 Directed COVID-19 therapy
134.4 Adjuvant therapy of severe acute respiratory syndrome coronavirus 2 infections
134.5 Anticoagulation therapy for hospitalized COVID-19 patients
134.6 Prophylaxis against COVID-19
134.7 Summary for pathogenesis-directed therapy of COVID-19
References
Chapter 135. COVID-19 laboratory diagnosis
Abstract
135.1 Background
135.2 Severe acute respiratory syndrome coronavirus 2 testing patients specimens types
135.3 Severe acute respiratory syndrome coronavirus 2 diagnostic assays
References
Chapter 136. CHITV: an updated combination treatment regimen for COVID-19
Abstract
136.1 Epidemiology and clinical manifestations
136.2 Combination therapy
136.3 Corticosteroids
136.4 Interferon
136.5 Vitamin C
136.6 Heparin
136.7 Thymosin
136.8 Other recommended interventions
136.9 Concluding remarks
References
Chapter 137. COVID-19 epidemiology and prevention
Abstract
137.1 Introduction
137.2 Epidemiology
137.3 Prevention
137.4 Future perspectives
References
Part 26: Fungal pathogenesis
Chapter 138. Classification of medically important fungi
Abstract
138.1 Introduction
138.2 Ascomycetes
138.3 Basidiomycetes
138.4 Zygomycetes
138.5 Microsporidia
138.6 Conclusions
References
Chapter 139. Pathogenesis of Pneumocystis infection
Abstract
Abbreviations and acronyms
139.1 Introduction
139.2 History, taxonomy, and morphology
139.3 Spectrum of infection
139.4 Epidemiology
139.5 Pathogenesis
139.6 Diagnosis
139.7 Treatment
139.8 Prevention
References
Chapter 140. Pathogenesis of fungal infections
Abstract
140.1 Introduction
140.2 Fungal pathogenicity
140.3 Host responses to fungi
140.4 Antifungal resistance
140.5 Determinants of fungal pathogenesis
140.6 Extracellular hydrolytic enzymes and proteins
140.7 Responses to multiple stresses
140.8 Synergistic coaggregation with resident microbiota
140.9 Conclusions
References
Chapter 141. Biology and pathogenesis of Enterocytozoon spp.
Abstract
141.1 Classification of Enterocytozoon spp.
141.2 Clinical significance of Enterocytozoon infections
141.3 E. bieneusi infection in immunocompromised persons
141.4 E. bieneusi infection in children
141.5 E. bieneusi infection in animals
141.6 E. hepatopenaei infection in shrimps
141.7 Molecular studies of pathogen–host interactions in Enterocytozoon spp.
141.8 Future perspectives
References
Chapter 142. Host immune responses to fungal infection
Abstract
142.1 Introduction
142.2 Galectin 3
142.3 Toll-like receptors 1, 2, and 6
142.4 Toll-like receptor 4
142.5 Toll-like receptor 9
142.6 Dectin-1
142.7 Dectin-2
142.8 Dectin-3
142.9 Mincle
142.10 Mannose receptor
142.11 DC-SIGN
142.12 Chitin immune recognition
Acknowledgments
References
Chapter 143. Mechanisms of antifungal resistance
Abstract
143.1 Introduction
143.2 Antifungal classes
143.3 Cellular targets for antifungals
143.4 Drug resistance
143.5 Concluding remarks
References
Part 27: Fungal infections
Chapter 144. Biology of the major human fungal pathogen Candida albicans
Abstract
144.1 Introduction
144.2 Morphological diversity
144.3 Biofilm development
144.4 Virulence factors: secreted aspartyl proteinases and phospholipases
144.5 Sexual reproduction
144.6 Conclusion
Acknowledgments
References
Chapter 145. Cryptococcus neoformans: life cycle, morphogenesis, and virulence
Abstract
145.1 Overview of Cryptococcus neoformans
145.2 Life cycle of Cryptococcus neoformans
145.3 Infection and pathogenicity of Cryptococcus neoformans
145.4 Virulence factors of Cryptococcus neoformans
References
Chapter 146. Superficial fungal infections
Abstract
146.1 Introduction
146.2 Dermatophytosis
146.3 Candidiasis
146.4 Pityriasis versicolor
146.5 Diagnosis of superficial mycoses
146.6 Advice on specimen collection
References
Part 28: Parasitic pathogenesis
Chapter 147. Classification of medically important parasites
Abstract
147.1 Introduction
147.2 Medically important protozoa and chromists
147.3 Medically important helminths
147.4 Medically important arthropods
147.5 Future perspectives
References
Chapter 148. Pathogenesis of protozoan infections
Abstract
148.1 Introduction
148.2 Protozoan invasion
148.3 Host–protozoa interactions
148.4 Pathophysiologies of protozoan infections
148.5 Conclusion
References
Chapter 149. Cestodes and cestodiasis
Abstract
149.1 Human pathogenic cestodes
149.2 Human cestodiasis
References
Chapter 150. Pathogenesis of trematode infections (blood, liver and lung flukes)
Abstract
150.1 Introduction
150.2 Blood flukes
150.3 Lung flukes
150.4 Liver flukes
150.5 Conclusions
References
Part 29: Protozoan infections
Chapter 151. Plasmodium
Abstract
151.1 Introduction
151.2 Life cycle of Plasmodium
151.3 Malaria infection and immunity
151.4 Pathogenesis and clinical symptoms
151.5 Diagnosis
151.6 Treatment
151.7 Prevention and control
151.8 Conclusion remarks
References
Chapter 152. Human babesiosis
Abstract
152.1 Introduction
152.2 Pathogen
152.3 Epidemiology
152.4 Clinical presentations and complications
152.5 Pathogenesis
152.6 Diagnosis
152.7 Treatment and prevention
Acknowledgments
References
Chapter 153. Molecular diagnosis of Toxoplasma gondii
Abstract
153.1 Toxoplasma gondii: the parasite and the disease
153.2 Genome characteristics of Toxoplasma
153.3 DNA extraction for Toxoplasma molecular diagnosis
153.4 Targets for Toxoplasma DNA amplification
153.5 Techniques and quality control for Toxoplasma DNA detection
153.6 Conclusions
References
Chapter 154. Leishmania
Abstract
154.1 Introduction
154.2 Classification and life cycle
154.3 Vector
154.4 Genome
154.5 Diseases manifestations
154.6 Detecting Leishmania in infections
154.7 Treatments and prevention
References
Chapter 155. Entamoeba
Abstract
155.1 Introduction
155.2 Pathophysiology of intestinal amebiasis and amebic liver abscess
155.3 Epidemiology of amebiasis
155.4 Morphology and life cycle of Entamoeba histolytica
155.5 Mechanisms of Entamoeba histolytica pathogenicity
155.6 Immunology of Entamoeba histolytica infections
155.7 Diagnosis of amebiasis
155.8 Treatment, and prevention of amebiasis
155.9 Future perspectives
Acknowledgments
References
Chapter 156. Cryptosporidium
Abstract
156.1 Introduction
156.2 Taxonomy
156.3 Structure
156.4 Life cycle
156.5 Epidemiology
156.6 Clinical disease and pathogenesis
156.7 Laboratory diagnosis
156.8 Treatment
156.9 Prevention
References
Chapter 157. Giardia and giardiasis
Abstract
157.1 Introduction
157.2 History and phylogenetics
157.3 Epidemiology
157.4 Clinical features, diagnosis, and treatment
157.5 Life cycle
157.6 Molecular pathogenesis
157.7 Immunology and immunobiology
157.8 Conclusion and future directions
References
Chapter 158. Naegleria
Abstract
158.1 Introduction
158.2 Generalities of the Naegleria genus
158.3 Molecular mechanisms of pathogenicity
158.4 Immune response
158.5 Diagnosis
158.6 Treatment
158.7 Future perspectives
References
Chapter 159. Parasitic infections of the central nervous system
Abstract
159.1 Introduction
159.2 Parasite taxonomy
159.3 Diagnosis of neuroinvasive parasitic diseases
159.4 Next generation sequencing for the diagnosis of neuroinvasive parasitic diseases
159.5 Protozoan infections
159.6 Nematode infections
159.7 Cestode infections
159.7.5 Coenurosis
159.7.6 Echinococcosis
159.7.7 Sparganosis
159.8 Trematode infections
159.9 Other, rare parasitic infections of the central nervous system
Acknowledgment
References
Part 30: Cestode and trematode infections
Chapter 160. Spirometra
Abstract
160.1 Introduction
160.2 Taxonomy
160.3 Morphology and genomics
160.4 Life cycle and epidemiology
160.5 Clinical features
160.6 Pathogenesis
160.7 Diagnosis
160.8 Treatment and prevention
160.9 Future perspectives
Acknowledgments
References
Chapter 161. Host immune responses to Taenia infection
Abstract
161.1 Taenia—a zoonotic parasite coevolved with human host
161.2 Parameters shaping host immune responses to Taenia infection
161.3 Innate immune response to Taenia infection
161.4 Cell-mediated immune response to Taenia infection
161.5 Humoral immune response to Taenia infection
161.6 Parasite modulation of host immune responses
References
Chapter 162. Immunological prophylaxes for Echinococcus granulosus infection
Abstract
162.1 Introduction
162.2 Host–parasite interactions
162.3 Protective antigens
162.4 Vaccination trials
162.5 Future perspectives
References
Chapter 163. Genomic and transcriptomic analyses of Clonorchis sinensis infection
Abstract
163.1 Introduction
163.2 Genomics
163.3 Transcriptomics
163.4 Future perspectives
References
Chapter 164. Schistosoma and schistosomiasis
Abstract
164.1 Introduction
164.2 Structure and biology of schistosomes
164.3 Epidemiology
164.4 Pathogenesis and immune response
164.5 Clinical features and relationship with other diseases
164.6 Diagnosis
164.7 Treatment, chemoprophylaxis, and prevention
164.8 Future perspectives
References
Chapter 165. Fasciola
Abstract
165.1 Introduction
165.2 Taxonomy, morphology, and genome
165.3 Life cycle and epidemiology
165.4 Clinical features
165.5 Pathogenesis
165.6 Diagnosis
165.7 Treatment and prevention
165.8 Future perspectives
References
Index

Yi-Wei Tang

Dr. Yi-Wei Tang is currently the Chief of the Clinical Microbiology Service at the Memorial Sloan-Kettering Cancer Center in New York City, USA. He was a Lecturer and Clinical Fellow at the Mayo Clinic and Assistant Professor, Associate Professor to Professor at the Vanderbilt University School of Medicine. He has been engaged in medical and molecular microbiology translational researches, aimed at developing and evaluating new and advanced microbiological diagnostic testing procedures. Dr. Tang ranks among the top of the scientific field in clinical and molecular microbiology, as evidenced by his election as an Editor for the Journal of Clinical Microbiology, an Associate Editor for the Journal of Molecular Diagnostics, and a Fellow of the American Academy for Microbiology and of the Infectious Disease Society of America. Dr. Tang has been recognized for his extraordinary expertise in the molecular microbiology diagnosis and monitoring with 156 peer-reviewed articles and 68 book chapters in this field during the past 20 years. Dr. Tang is a chief editor of a Springer book “Advanced Techniques in Diagnostic Microbiology” and a co-editor of two ASM Press books “Molecular Microbiology: Diagnostic Principle and Practice” and “Diagnostic Microbiology in Immunocompromised Host”.

Affiliations and expertise

Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Musa Hindiyeh

Dr. Hindiyeh is the Director of Augusta Victoria Hospital Department of Laboratory Medicine and the Laboratory Department of Caritas Baby Hospital. Before his appointment at Augusta Victoria Hospital, he was the director of the Rapid Viral Molecular Diagnostic Unit at the Israel Central Virology Laboratory. Dr. Hindiyeh received his Bachelor’s degree in Medical Technology and his Doctoral degree in Microbiology and Immunology from the University of Arkansas for Medical Sciences. He later received postdoctoral training in Medical Microbiology and Public Health from the University of Utah. Dr. Hindiyeh has double American boards certifications. One from the American Society of Clinical Pathology and one from the American Society of Microbiology (American Board in Medical Microbiology). Dr. Hindiyeh is currently a member of the Palestinian National Immunization Technical Advisory Committee and is a member of the Measles elimination committee. Dr. Hindiyeh has been interested in developing rapid viral and bacterial diagnostic assays in addition to researching the emergence and spread of antibiotic resistant bacteria.

Affiliations and expertise

Director of Augusta Victoria Hospital Department of Laboratory Medicine and the Laboratory Department of Caritas Baby Hospital

Dongyou Liu

Dongyou Liu, PhD, undertook his veterinary science education at Hunan Agricultural University, China, and pursued postgraduate training at the University of Melbourne, Australia. Over the past two decades, he has worked at several research and clinical laboratories in Australia and the United States of America, with focuses on molecular characterization and virulence determination of microbial pathogens such as ovine footrot bacterium (Dichelobacter nodosus), dermatophyte fungi (Trichophyton, Microsporum and Epidermophyton) and listeriae (Listeria species) as well as security sensitive biological agents. He is the first author of >50 original research and review articles in various international journals, the contributor of 122 book chapters, and the editor of recently released “Handbook of Listeria monocytogenes” (2008), “Handbook of Nucleic Acid Purification” (2009), “Molecular Detection of Foodborne Pathogens” (2009), “Molecular Detection of Human Viral Pathogens” (2010), “Molecular Detection of Human Bacterial Pathogens” (2011), “Molecular Detection of Human Fungal Pathogens” (2011), and “Molecular Detection of Human Parasitic Pathogens” (2012), all of which are published by CRC Press.

Affiliations and expertise

Prince of Wales Hospital, NSW, Australia

Andrew Sails

Dr Andrew Sails is a Consultant Clinical Scientist at the Public Health England Microbiology Services Laboratory in Newcastle upon Tyne, where he is Head of Molecular Diagnostics and Research and Development. He graduated in Biology from Manchester University in 1991 and began his clinical microbiology career at Preston Public Health Laboratory. Further postgraduate study resulted in a Masters degree in Biomedical Science from Manchester Metropolitan University and a PhD in Medical Microbiology from the University of Central Lancashire. He carried out postdoctoral research the Centers for Disease Control and Prevention (CDC) in Atlanta, USA research into the development of DNA sequence-based subtyping of Campylobacter and other pathogenic foodborne bacteria. He returned to the UK in 2003 to take up his current post at Newcastle, where is Head of Molecular Diagnostics and leads the development and evaluation of new technology and methods for microbiological diagnosis, identification and typing of microbial pathogens. In 2004 he was awarded the W.H. Pierce Memorial Prize for outstanding contributions to bacteriology by The Society for Applied Microbiology.

He has worked extensively in the area of molecular diagnostics and molecular epidemiology of infectious disease (M. tuberculosis, Campylobacter and C. difficile in particular) and has published in these areas. His current research interests include the detection and fingerprinting of pathogens and the application of molecular biology to clinical microbiology to aid the diagnosis and management of infectious disease. He has served on the editorial board of several journals including Applied and Environmental Microbiology, the Journal of Clinical Microbiology and the Open Microbiology Journal. He is a member of several learned societies including Society for Applied Microbiology, The Federation of Clinical Scientists, The Association of Clinical Biochemistry and Laboratory Medicine and is an affiliate member of the Royal College of Pathologists. Since 2005 he has been a member of The Society for Applied Microbiology Executive Committee and is currently serving as its Honorary Meetings Secretary. He was also recently appointed as a Visiting Fellow at Northumbria University where he is contributes to undergraduate and postgraduate teaching and PhD supervision.

Affiliations and expertise

ODx Innovations, Solasta House, The Inverness Campus, Inverness, United Kingdom

Paul Spearman

Paul Spearman, MD is the Albert B. Sabin Professor and Director of Infectious Diseases at Cincinnati Children’s Hospital Medical Center. His laboratory studies fundamental aspects of HIV biology and develops new vaccines for human pathogens. HIV assembly processes are a major focus of the laboratory, including the trafficking of the HIV envelope glycoprotein and its interaction with essential host factors. A related project studies how HIV interacts with macrophages and microglia. Dr. Spearman and his colleagues in the CCHMC Vaccine and Treatment Evaluation Unit (VTEU) are engaged in the design and performance of clinical trials for new vaccines in adults and children, with a special interest in employing cutting-edge technologies to define innate and adaptive immune responses to vaccines. Dr. Spearman is currently leading trials for Ebola and RSV vaccine development. Dr. Spearman serves on the Board of Scientific Counselors for NCI, the Vaccines and Related Biological Products Advisory Committee for the FDA, and is Past President of the Pediatric Infectious Diseases Society (PIDS). Beyond his research interests, Dr. Spearman is a Pediatric ID clinician and enjoys caring for children and mentoring future leaders in Infectious Diseases.

Affiliations and expertise

Albert B. Sabin Professor and Director of Infectious Diseases, Cincinnati Children’s Hospital, USA

Jing-Ren Zhang

Jingren Zhang was educated at Gansu Agricultural University and National Standard Institute for Veterinary Bio-Products in China followed by a PhD from the University of Texas Health Science Center and a postdoctoral fellowship at St. Jude Children’s Research Hospital in Memphis. He served as Assistant Professor at Albany Medical College before taking his current post at Tsinghua University School of Medicine.

Affiliations and expertise

Professor and Vice Dean, Tsinghua University School of Medicine, Beijing, China

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

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Molecular Medical Microbiology

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Yi-Wei Tang

Musa Hindiyeh

Dongyou Liu

Andrew Sails

Paul Spearman

Jing-Ren Zhang