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Staphylococcus aureus - Microbiology, Pathology, Immunology, Therapy and Prophylaxis
Fabio Bagnoli, Rino Rappuoli, Guido Grandi
Verlag Springer-Verlag, 2018
ISBN 9783319720630 , 543 Seiten
Format PDF, OL
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Staphylococcus aureus - Microbiology, Pathology, Immunology, Therapy and Prophylaxis
Declaration of Interest
6
Authorship
6
Preface
7
Contents
10
5 Carriage, Clinical Microbiology and Transmission of Staphylococcus aureus
12
Abstract
12
1 Clinical Microbiology
13
1.1 Introduction of Rapid Molecular Detection Methodologies
15
1.2 Enhancing Culture-based Techniques
15
1.3 Replacing Culture-based Techniques
16
1.4 Point-of-Care Technologies
18
2 S. aureus Carriage
18
3 S. aureus Transmission
20
3.1 MRSA Transmission in the Hospital
21
3.2 Preventing MRSA Transmission
22
3.3 MRSA Transmission in the Community
23
4 Summary
25
References
25
3 Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus
31
Abstract
31
1 Introduction
33
2 General Epidemiology of S. aureus
34
3 Molecular Epidemiology
35
3.1 Molecular Typing Methods
35
3.1.1 Pulsed-Field Gel Electrophoresis (PFGE)
35
3.1.2 Multilocus Sequence Typing (MLST)
36
3.1.3 Staphylococcal Protein A (spa) Typing
36
3.1.4 SCCmec Typing
36
3.1.5 Whole Genome Sequencing (WGS)
37
3.2 Worldwide Distribution of the Principal Clones and Lineages
38
3.2.1 Healthcare-Associated MRSA
38
3.2.2 CA-MRSA
42
3.2.3 LA-MRSA
45
3.2.4 Molecular Epidemiology of MSSA
46
4 S. aureus and Antibiotic Resistance
47
4.1 Vancomycin
48
4.2 Linezolid
51
4.3 Daptomycin
52
5 Conclusions
53
Acknowledgments
53
References
54
5018 Structure and Function of Surface Polysaccharides of Staphylococcus aureus
67
Abstract
67
1 Introduction
69
2 Capsular Polysaccharides (CPs)
69
2.1 Structures of CP5 and CP8
70
2.2 Biosynthesis of CP
70
2.3 Nontypeable S. aureus Isolates
73
2.4 Regulation of CP Biosynthesis
74
2.5 Role of S. aureus CPs in Virulence
76
2.6 CP5 and CP8 as Vaccine Components
77
3 Wall Teichoic Acid (WTA)
78
3.1 Structure of WTA
78
3.2 Biosynthesis of WTA
79
3.3 Regulation of WTA Biosynthesis
81
3.4 Role of WTA in S. aureus Physiology
82
3.5 Role of WTA as Phage Receptor and Glycocode for Horizontal Gene Transfer
83
3.6 Role of WTA in Antibiotic Resistance and WTA Inhibitory Compounds
84
3.7 Role of WTA in Colonization and Virulence
85
3.8 WTA as a Vaccine Candidate
87
4 Polysaccharide Intercellular Adhesin (PIA)/Poly-N-Acetyl Glucosamine (PNAG)
87
4.1 Structure of PIA/PNAG
88
4.2 Biosynthesis of PIA/PNAG
89
4.3 Regulation of PIA/PNAG Biosynthesis
89
4.4 Role of PIA/PNAG in Virulence
90
4.5 PIA/PNAG as a Vaccine Candidate
90
5 Conclusions
91
References
92
5002 Cell Wall-Anchored Surface Proteins of Staphylococcus aureus: Many Proteins, Multiple Functions
104
Abstract
104
1 Introduction
105
2 CWA Surface Protein Secretion and Surface Display
106
2.1 Secretion
106
2.2 Sorting
106
3 Cell Wall-Anchored Protein Structure and Function
108
3.1 The MSCRAMM Family
108
3.1.1 Structure
108
3.1.2 Ligand Binding: Dock, Lock, and Latch
108
3.1.3 Ligand Binding: The Collagen Hug
112
3.1.4 Post-Translational Modification
113
3.2 G5-E Repeat Domains
115
3.3 Three-Helical Bundles
116
3.4 The NEAT Motif Family
116
3.5 The Legume Lectin Domain
117
3.6 Fibronectin Binding by Tandem ?-Zipper
117
3.7 Nucleotidase Motif
118
4 CWA Proteins as Colonization and Virulence Factors
119
4.1 Approaches to Elucidating the Contribution of CWA Proteins to the Virulence of S. aureus
119
4.2 CWA Proteins Promote Colonization of the Host
121
4.3 CWA Protein Interactions with Fibrinogen/Fibrin
122
5 Discussion and Future Prospects
123
References
124
16 Staphylococcus aureus Pore-Forming Toxins
130
Abstract
130
1 Identification of S. aureus Toxins: An Overview
131
1.1 Alpha-Toxin: The Prototypical Beta-Barrel Pore-Forming Toxin
133
2 Beta-Barrel Bicomponent Pore-Forming Leukocidins
134
2.1 Panton–Valentine Leukocidin (LukSF-PV/PVL)
134
2.2 Gamma-Hemolysin HlgACB
135
2.3 Leukocidin ED (LukED)
135
2.4 Leukocidin AB (LukAB)
136
3 Mode of Action of S. aureus Beta-Barrel Pore-Forming Leukocidins
137
4 Identification of Proteinaceous Cellular Receptors for the Leukocidins
139
4.1 Alpha-Toxin and ADAM10
140
4.2 LukED: CCR5, CXCR1, CXCR2, and DARC
141
4.3 LukSF-PV/PVL: C5aR and C5L2
143
4.4 HlgAB: CXCR1, CXCR2, CCR2, and DARC
143
4.5 HlgCB: C5aR and C5L2
144
4.6 LukAB: CD11b
144
5 Toxin Redundancy
146
6 Conclusions
147
Acknowledgments and/or funding sources:
147
References
147
5019 The Role of Two-Component Signal Transduction Systems in Staphylococcus aureus Virulence Regulation
154
Abstract
154
1 Introduction
155
2 Global Regulators of Virulence Expression
158
2.1 AgrCA
158
2.1.1 Molecular Basis of Agr Regulation
158
2.1.2 Agr and Virulence Regulation
162
2.2 SaeRS
164
2.2.1 Molecular Basis of SaeRS
164
2.2.2 SaeRS and Virulence Regulation
166
3 Response to AMPs and Cell Wall Damage
168
3.1 VraSR
168
3.2 GraXSR
172
3.3 BraRS
174
4 Cell Wall Metabolism, Autolysis and Cell Death
175
4.1 WalRK
176
4.2 ArlRS
179
4.3 LytSR
180
5 Respiration, Fermentation and Nitrate Metabolism
182
5.1 SrrAB
182
5.2 NreCBA
185
5.3 AirRS
186
6 Nutrient Sensing and Metabolism
188
6.1 HssSR
188
6.2 KdpDE
189
6.3 PhoRP
191
7 Conclusions
192
References
192
32 Staphylococcus aureus-Associated Skin and Soft Tissue Infections: Anatomical Localization, Epidemiology, Therapy and Potential Prophylaxis
208
Abstract
208
1 Introduction
210
2 Human Skin Anatomy
211
3 Overview of SSTIs
213
3.1 Superficial Skin Infections—Impetigo and Ecthyma
213
3.2 Follicular Infections—Folliculitis, Furunculosis, Carbunculosis
216
3.3 Intradermal Infections—Erysipelas, Cellulitis, Necrotizing Fasciitis
217
4 Epidemiology of Staphylococcus aureus SSTIs
217
4.1 Community-Acquired SSTIs
217
4.2 Surgical Site Infections (SSIs)
218
4.3 Affected Populations and Medical Cost of Hospitalizations Associated with SA-SSTIs
221
4.4 Paediatric SA-SSTIs
222
5 Virulence Factors and Pathogenesis of S. aureus-Associated Skin Infections
223
6 Therapy for SA-SSTIs
225
7 Prevention of SA-SSTIs
225
8 Discussion
228
Acknowledgments
228
References
229
19 Staphylococcus aureus-Associated Musculoskeletal Infections
237
Abstract
237
1 Introduction
238
2 Staphylococcus aureus Osteomyelitis
238
2.1 Epidemiology
238
2.2 Pathogenesis
239
2.2.1 General Pathogenesis and Classification
239
2.2.2 Molecular and Cellular Pathogenesis
241
2.3 Clinical Manifestations and Diagnosis
245
2.4 Special Forms of Osteomyelitis
248
2.4.1 Vertebral Osteomyelitis
248
2.4.2 Postoperative Sternum Osteomyelitis
249
2.5 Management
250
3 Staphylococcus aureus Infections of Native Joints
256
4 Staphylococcus aureus Pyomyositis
259
5 Conclusions
260
References
261
5001 Bacteremia, Sepsis, and Infective Endocarditis Associated with Staphylococcus aureus
270
Abstract
270
1 Introduction
271
2 Staphylococcus aureus Bacteremia
271
2.1 Epidemiology
271
2.2 Clinical Manifestations and Outcomes
274
2.3 Management
277
3 Staphylococcus aureus Infective Endocarditis
284
3.1 Epidemiology
284
3.2 Prosthetic Valve Endocarditis
285
3.3 Pathophysiology
285
3.4 Clinical Manifestations and Outcomes
286
3.5 Management
287
4 Conclusions
290
Acknowledgements
290
References
290
2 Amphixenosic Aspects of Staphylococcus aureus Infection in Man and Animals
304
Abstract
304
1 Introduction
305
2 Factors Influencing Prevalence of Staphylococcal Amphixenoses and Related Risks
307
3 The Role of Companion Animals in the Amphixenosic Transmission of S. aureus
311
4 The Amphixenosic Transmission of S. aureus: Human Versus Pet Animals and Vice Versa
316
5 The Epidemiology of Livestock-Associated S. aureus: The Role of Bovine Milk and Dairy Cattle
318
6 Livestock-Associated S. aureus: The Role of Swine and Chickens
319
7 Conclusions
321
8 Future Directions
322
References
322
42 Treatment of Staphylococcus aureus Infections
331
Abstract
331
1 Introduction
333
2 Guidelines for Therapy of S. aureus Infections
339
3 General Considerations for Therapy of S. aureus Infections
340
3.1 Noninvasive Skin and Soft Tissue Infections
340
3.2 Invasive Infections
347
4 Considerations in the Therapy of Specific Clinical Syndromes
349
4.1 Bacteremia
349
4.2 Endocarditis and Intravascular Infection
353
4.3 Pneumonia
354
4.4 Osteomyelitis, Including Discitis
356
4.5 Epidural Abscess
358
4.6 Septic Arthritis
359
4.7 Pyomyositis
360
4.8 Necrotizing Fasciitis
362
4.9 Impetigo
363
4.10 Mastitis and Breast Abscess
363
4.11 Conjunctivitis
364
4.12 Orbital Infections
364
4.13 Endophthalmitis and Panophthalmitis
365
4.14 Parotitis
366
4.15 Toxinoses
366
4.15.1 Staphylococcal Toxic Shock Syndrome (TSS)
366
4.15.2 Staphylococcal Scalded Skin Syndrome (SSSS)
367
4.16 Urogenital Infections
368
4.17 Lemierre’s Syndrome
369
4.18 Meningitis and Other CNS Infections
369
5 Conclusions
371
References
372
5004 The Innate Immune Response Against Staphylococcus aureus
390
Abstract
390
1 Introduction
391
2 The Encounter at the Epithelial Barrier
393
2.1 The Sentinel Function of Toll-like Receptor-2: Permitting Colonization and Preventing Invasion
394
2.2 Bacterial Invasion: Immune Defense Relies on Intracellular Sensors and Inflammasome Activation
396
2.3 Linking Inflammasomes to Protective T Cell Responses: The Role of NLRP3 in Th17 Differentiation
397
3 Professional Phagocytes and Their Effector Functions
398
3.1 Phagocytosis: Linking Intracellular Lysis to Antigen Presentation
398
3.2 Tissue-resident Phagocytes
400
3.2.1 Mast Cells: Well-prepared Guardians of Skin and Mucosa
400
3.2.2 Macrophages: Tissue-Specific Vigilants Balancing the Local Immune Response
400
3.3 Blood-Derived Phagocytes
401
3.3.1 Neutrophils: Recruited to Resolve Uncontrolled Spread of Infection
402
3.4 Dendritic Cells: Orchestrating the Adaptive Immune Response in Tissue and Lymph Nodes
403
3.4.1 Myeloid Dendritic Cells: Expert Control of T Cell Responses
403
3.4.2 Plasmacytoid Dendritic Cells and Type I Interferons: Fine-Tuning of Innate and Adaptive Immune Responses
404
4 The Last Frontiers Before Adaptive Immunity
405
4.1 Innate Immune B Cells: Rapid Supply of Antibacterial Antibodies
405
4.2 Natural Killer Cells: Neglected Sensors for Intracellular Persisting S. aureus?
406
4.3 Innate Lymphoid Cells: Confinement of S. aureus to Its Niche?
407
5 Conclusion
407
References
410
1 Adaptive Immunity Against Staphylococcus aureus
424
Abstract
424
1 Introduction
425
2 Immunological Overview
425
3 Role of B Cells and Antibodies
426
3.1 Preexisting Antibodies as Immunologic Correlates for Protection
427
3.2 Role of Antibodies in Vaccine-Mediated Protection
427
3.3 Evasion Mechanisms from the Humoral Immune Response
429
4 Role of T Cells
430
4.1 Th1 Cells
431
4.2 Th2 Cells
432
4.3 Th17 Cells
433
4.4 Regulatory T Cells
435
5 Conclusion
435
Acknowledgements
436
References
436
5017 Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation
445
Abstract
445
1 Introduction
447
2 The Mechanisms of Immune Evasion
448
3 Conserved Structural Properties of Evasion Molecules: A Structure–Function Analysis
451
3.1 Proteins Consisting of an OB-Fold and/or ?-Grasp Domain
453
3.1.1 The Superantigens
454
3.1.2 Superantigen-like Proteins
455
3.1.3 The EAP Domain Proteins
457
3.1.4 Chemotaxis Inhibitory Protein of S. aureus
457
3.1.5 FPR2 Inhibitory Proteins
458
3.1.6 Staphylokinase
458
3.1.7 Staphylococcal Nuclease
459
3.2 Proteins Consisting of a Triple Alpha Helix
459
3.2.1 The Immunoglobulin-Binding Proteins
459
3.2.2 The Staphylococcal Complement Inhibitor Family
460
3.2.3 The Extracellular Fibrinogen-Binding Protein Family
461
3.2.4 Staphylococcal Coagulases
461
3.3 The Staphylococcal Toxins: ?-Barrel Pore-Formers and ?-Helices
462
3.3.1 The ?-Barrel Pore-Forming Toxins
462
3.3.2 The Phenol-Soluble Modulins
464
3.4 Additional Secreted Enzymes
465
3.4.1 Staphylococcal Proteases
465
3.4.2 ?-Hemolysin
465
3.5 The Structure–Function Relationship
466
4 Genomic Location and Host Specificity
467
4.1 Core Variable Genome
468
4.1.1 Genomic Islands
468
4.1.2 Immune Evasion Cluster 2 (IEC2)
471
4.1.3 Other Clustered Immune Evasion Genes
472
4.2 Mobile Genetic Elements
473
4.2.1 SaPIs
473
4.2.2 Prophages
474
4.3 Host Adaptation of Immune Evasion Molecules
476
5 Future Perspectives
477
5.1 Therapeutic Strategies Based on Evasion Molecules for S. aureus Infections
477
5.2 Therapeutic Strategies for Other Inflammatory Conditions and Cancer
479
6 Conclusions
480
Acknowledgements
480
References
481
54 Vaccines for Staphylococcus aureus and Target Populations
494
Abstract
494
1 Introduction
496
2 Rationale Behind the Need of a S. Aureus Vaccine
498
3 Target Populations Suitable for S. Aureus Vaccine Efficacy Trials
500
3.1 End-Stage Renal Disease (ESRD) Patients
500
3.2 Intensive Care Unit (ICU) Patients
508
3.3 Surgery Patients
508
3.4 Community-Acquired Skin and Soft Tissue Infections (CA-SSTIs) Patients
509
4 Preclinical Research on Antigens Selected for Clinical Development
511
4.1 Antigens that Reached Phase III Trials
511
4.2 Antigens Currently Being Tested in Phase II Trials
512
4.3 Antigen Combinations that Reached Phase I Trials
513
4.4 Recently Proposed Antigens that Are Still in Preclinical Phase
514
5 Clinical Data on Vaccine Candidates that Reached Phase III
516
5.1 Summary of Phase I–III Trial Data on V710
516
5.2 Summary of Phase I–III Trial Data on StaphVax
517
6 Lack of Established Correlates of Protection
519
7 Discussion
521
Acknowledgments
522
References
523
5005 Lysin Therapy for Staphylococcus aureus and Other Bacterial Pathogens
532
Abstract
532
1 Introduction
533
2 Mechanism of Action
534
3 Lysin Efficacy
536
4 Staphylococcus aureus-Specific Lysins
536
5 Synergy
537
6 Biofilms
538
7 Effects of Antibodies
538
8 Bacterial Resistance to Lysins
539
9 Conclusion
540
Acknowledgments
541
Literature Cited
541