Bagnoli / Rappuoli / Grandi Staphylococcus aureus

Microbiology, Pathology, Immunology, Therapy and Prophylaxis
1. Auflage 2018
ISBN: 978-3-319-72063-0
Verlag: Springer Nature Switzerland
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 543 Seiten

Reihe: Biomedical and Life Sciences (R0)

This volume offers a comprehensive overview of basic and applied aspects of Staphylococcus aureus, which is one of the most important human pathogens. It includes sixteen chapters that address the microbiology and immunology of S. aureus, the pathology of its key manifestations, and the current standard of care. Further, it reviews cutting-edge advances in alternative therapeutic and prophylactic approaches to antibiotics. All chapters were written by respected experts in the field - presenting recent findings on a diverse range of aspects, they are nonetheless interlinked. As such, the book is a must-read for all researchers, clinicians and technicians engaged in basic or applied science work involving S. aureus. 

Fabio BagnoliGSK Vaccines, Siena, Italye-mail: [e-mail]
Rino RappuoliGSK Vaccines, Siena, Italye-mail: [e-mail]
Guido GrandiUniversity of Trento, Povo, Italye-mail: [e-mail]

Autoren/Hrsg.

Bagnoli, Fabio

Rappuoli, Rino

Grandi, Guido

Inhaltsverzeichnis

1;Declaration of Interest;6
1.1;Authorship;6
2;Preface;7
3;Contents;10
4;5 Carriage, Clinical Microbiology and Transmission of Staphylococcus aureus;12
4.1;Abstract;12
4.2;1 Clinical Microbiology;13
4.2.1;1.1 Introduction of Rapid Molecular Detection Methodologies;15
4.2.2;1.2 Enhancing Culture-based Techniques;15
4.2.3;1.3 Replacing Culture-based Techniques;16
4.2.4;1.4 Point-of-Care Technologies;18
4.3;2 S. aureus Carriage;18
4.4;3 S. aureus Transmission;20
4.4.1;3.1 MRSA Transmission in the Hospital;21
4.4.2;3.2 Preventing MRSA Transmission;22
4.4.3;3.3 MRSA Transmission in the Community;23
4.5;4 Summary;25
4.6;References;25
5;3 Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus;31
5.1;Abstract;31
5.2;1 Introduction;33
5.3;2 General Epidemiology of S. aureus;34
5.4;3 Molecular Epidemiology;35
5.4.1;3.1 Molecular Typing Methods;35
5.4.1.1;3.1.1 Pulsed-Field Gel Electrophoresis (PFGE);35
5.4.1.2;3.1.2 Multilocus Sequence Typing (MLST);36
5.4.1.3;3.1.3 Staphylococcal Protein A (spa) Typing;36
5.4.1.4;3.1.4 SCCmec Typing;36
5.4.1.5;3.1.5 Whole Genome Sequencing (WGS);37
5.4.2;3.2 Worldwide Distribution of the Principal Clones and Lineages;38
5.4.2.1;3.2.1 Healthcare-Associated MRSA;38
5.4.2.2;3.2.2 CA-MRSA;42
5.4.2.3;3.2.3 LA-MRSA;45
5.4.2.4;3.2.4 Molecular Epidemiology of MSSA;46
5.5;4 S. aureus and Antibiotic Resistance;47
5.5.1;4.1 Vancomycin;48
5.5.2;4.2 Linezolid;51
5.5.3;4.3 Daptomycin;52
5.6;5 Conclusions;53
5.7;Acknowledgments;53
5.8;References;54
6;5018 Structure and Function of Surface Polysaccharides of Staphylococcus aureus;67
6.1;Abstract;67
6.2;1 Introduction;69
6.3;2 Capsular Polysaccharides (CPs);69
6.3.1;2.1 Structures of CP5 and CP8;70
6.3.2;2.2 Biosynthesis of CP;70
6.3.3;2.3 Nontypeable S. aureus Isolates;73
6.3.4;2.4 Regulation of CP Biosynthesis;74
6.3.5;2.5 Role of S. aureus CPs in Virulence;76
6.3.6;2.6 CP5 and CP8 as Vaccine Components;77
6.4;3 Wall Teichoic Acid (WTA);78
6.4.1;3.1 Structure of WTA;78
6.4.2;3.2 Biosynthesis of WTA;79
6.4.3;3.3 Regulation of WTA Biosynthesis;81
6.4.4;3.4 Role of WTA in S. aureus Physiology;82
6.4.5;3.5 Role of WTA as Phage Receptor and Glycocode for Horizontal Gene Transfer;83
6.4.6;3.6 Role of WTA in Antibiotic Resistance and WTA Inhibitory Compounds;84
6.4.7;3.7 Role of WTA in Colonization and Virulence;85
6.4.8;3.8 WTA as a Vaccine Candidate;87
6.5;4 Polysaccharide Intercellular Adhesin (PIA)/Poly-N-Acetyl Glucosamine (PNAG);87
6.5.1;4.1 Structure of PIA/PNAG;88
6.5.2;4.2 Biosynthesis of PIA/PNAG;89
6.5.3;4.3 Regulation of PIA/PNAG Biosynthesis;89
6.5.4;4.4 Role of PIA/PNAG in Virulence;90
6.5.5;4.5 PIA/PNAG as a Vaccine Candidate;90
6.6;5 Conclusions;91
6.7;References;92
7;5002 Cell Wall-Anchored Surface Proteins of Staphylococcus aureus: Many Proteins, Multiple Functions;104
7.1;Abstract;104
7.2;1 Introduction;105
7.3;2 CWA Surface Protein Secretion and Surface Display;106
7.3.1;2.1 Secretion;106
7.3.2;2.2 Sorting;106
7.4;3 Cell Wall-Anchored Protein Structure and Function;108
7.4.1;3.1 The MSCRAMM Family;108
7.4.1.1;3.1.1 Structure;108
7.4.1.2;3.1.2 Ligand Binding: Dock, Lock, and Latch;108
7.4.1.3;3.1.3 Ligand Binding: The Collagen Hug;112
7.4.1.4;3.1.4 Post-Translational Modification;113
7.4.2;3.2 G5-E Repeat Domains;115
7.4.3;3.3 Three-Helical Bundles;116
7.4.4;3.4 The NEAT Motif Family;116
7.4.5;3.5 The Legume Lectin Domain;117
7.4.6;3.6 Fibronectin Binding by Tandem ?-Zipper;117
7.4.7;3.7 Nucleotidase Motif;118
7.5;4 CWA Proteins as Colonization and Virulence Factors;119
7.5.1;4.1 Approaches to Elucidating the Contribution of CWA Proteins to the Virulence of S. aureus;119
7.5.2;4.2 CWA Proteins Promote Colonization of the Host;121
7.5.3;4.3 CWA Protein Interactions with Fibrinogen/Fibrin;122
7.6;5 Discussion and Future Prospects;123
7.7;References;124
8;16 Staphylococcus aureus Pore-Forming Toxins;130
8.1;Abstract;130
8.2;1 Identification of S. aureus Toxins: An Overview;131
8.2.1;1.1 Alpha-Toxin: The Prototypical Beta-Barrel Pore-Forming Toxin;133
8.3;2 Beta-Barrel Bicomponent Pore-Forming Leukocidins;134
8.3.1;2.1 Panton–Valentine Leukocidin (LukSF-PV/PVL);134
8.3.2;2.2 Gamma-Hemolysin HlgACB;135
8.3.3;2.3 Leukocidin ED (LukED);135
8.3.4;2.4 Leukocidin AB (LukAB);136
8.4;3 Mode of Action of S. aureus Beta-Barrel Pore-Forming Leukocidins;137
8.5;4 Identification of Proteinaceous Cellular Receptors for the Leukocidins;139
8.5.1;4.1 Alpha-Toxin and ADAM10;140
8.5.2;4.2 LukED: CCR5, CXCR1, CXCR2, and DARC;141
8.5.3;4.3 LukSF-PV/PVL: C5aR and C5L2;143
8.5.4;4.4 HlgAB: CXCR1, CXCR2, CCR2, and DARC;143
8.5.5;4.5 HlgCB: C5aR and C5L2;144
8.5.6;4.6 LukAB: CD11b;144
8.6;5 Toxin Redundancy;146
8.7;6 Conclusions;147
8.8;Acknowledgments and/or funding sources:;147
8.9;References;147
9;5019 The Role of Two-Component Signal Transduction Systems in Staphylococcus aureus Virulence Regulation;154
9.1;Abstract;154
9.2;1 Introduction;155
9.3;2 Global Regulators of Virulence Expression;158
9.3.1;2.1 AgrCA;158
9.3.1.1;2.1.1 Molecular Basis of Agr Regulation;158
9.3.1.2;2.1.2 Agr and Virulence Regulation;162
9.3.2;2.2 SaeRS;164
9.3.2.1;2.2.1 Molecular Basis of SaeRS;164
9.3.2.2;2.2.2 SaeRS and Virulence Regulation;166
9.4;3 Response to AMPs and Cell Wall Damage;168
9.4.1;3.1 VraSR;168
9.4.2;3.2 GraXSR;172
9.4.3;3.3 BraRS;174
9.5;4 Cell Wall Metabolism, Autolysis and Cell Death;175
9.5.1;4.1 WalRK;176
9.5.2;4.2 ArlRS;179
9.5.3;4.3 LytSR;180
9.6;5 Respiration, Fermentation and Nitrate Metabolism;182
9.6.1;5.1 SrrAB;182
9.6.2;5.2 NreCBA;185
9.6.3;5.3 AirRS;186
9.7;6 Nutrient Sensing and Metabolism;188
9.7.1;6.1 HssSR;188
9.7.2;6.2 KdpDE;189
9.7.3;6.3 PhoRP;191
9.8;7 Conclusions;192
9.9;References;192
10;32 Staphylococcus aureus-Associated Skin and Soft Tissue Infections: Anatomical Localization, Epidemiology, Therapy and Potential Prophylaxis;208
10.1;Abstract;208
10.2;1 Introduction;210
10.3;2 Human Skin Anatomy;211
10.4;3 Overview of SSTIs;213
10.4.1;3.1 Superficial Skin Infections—Impetigo and Ecthyma;213
10.4.2;3.2 Follicular Infections—Folliculitis, Furunculosis, Carbunculosis;216
10.4.3;3.3 Intradermal Infections—Erysipelas, Cellulitis, Necrotizing Fasciitis;217
10.5;4 Epidemiology of Staphylococcus aureus SSTIs;217
10.5.1;4.1 Community-Acquired SSTIs;217
10.5.2;4.2 Surgical Site Infections (SSIs);218
10.5.3;4.3 Affected Populations and Medical Cost of Hospitalizations Associated with SA-SSTIs;221
10.5.4;4.4 Paediatric SA-SSTIs;222
10.6;5 Virulence Factors and Pathogenesis of S. aureus-Associated Skin Infections;223
10.7;6 Therapy for SA-SSTIs;225
10.8;7 Prevention of SA-SSTIs;225
10.9;8 Discussion;228
10.10;Acknowledgments;228
10.11;References;229
11;19 Staphylococcus aureus-Associated Musculoskeletal Infections;237
11.1;Abstract;237
11.2;1 Introduction;238
11.3;2 Staphylococcus aureus Osteomyelitis;238
11.3.1;2.1 Epidemiology;238
11.3.2;2.2 Pathogenesis;239
11.3.2.1;2.2.1 General Pathogenesis and Classification;239
11.3.2.2;2.2.2 Molecular and Cellular Pathogenesis;241
11.3.3;2.3 Clinical Manifestations and Diagnosis;245
11.3.4;2.4 Special Forms of Osteomyelitis;248
11.3.4.1;2.4.1 Vertebral Osteomyelitis;248
11.3.4.2;2.4.2 Postoperative Sternum Osteomyelitis;249
11.3.5;2.5 Management;250
11.4;3 Staphylococcus aureus Infections of Native Joints;256
11.5;4 Staphylococcus aureus Pyomyositis;259
11.6;5 Conclusions;260
11.7;References;261
12;5001 Bacteremia, Sepsis, and Infective Endocarditis Associated with Staphylococcus aureus;270
12.1;Abstract;270
12.2;1 Introduction;271
12.3;2 Staphylococcus aureus Bacteremia;271
12.3.1;2.1 Epidemiology;271
12.3.2;2.2 Clinical Manifestations and Outcomes;274
12.3.3;2.3 Management;277
12.4;3 Staphylococcus aureus Infective Endocarditis;284
12.4.1;3.1 Epidemiology;284
12.4.2;3.2 Prosthetic Valve Endocarditis;285
12.4.3;3.3 Pathophysiology;285
12.4.4;3.4 Clinical Manifestations and Outcomes;286
12.4.5;3.5 Management;287
12.5;4 Conclusions;290
12.6;Acknowledgements;290
12.7;References;290
13;2 Amphixenosic Aspects of Staphylococcus aureus Infection in Man and Animals;304
13.1;Abstract;304
13.2;1 Introduction;305
13.3;2 Factors Influencing Prevalence of Staphylococcal Amphixenoses and Related Risks;307
13.4;3 The Role of Companion Animals in the Amphixenosic Transmission of S. aureus;311
13.5;4 The Amphixenosic Transmission of S. aureus: Human Versus Pet Animals and Vice Versa;316
13.6;5 The Epidemiology of Livestock-Associated S. aureus: The Role of Bovine Milk and Dairy Cattle;318
13.7;6 Livestock-Associated S. aureus: The Role of Swine and Chickens;319
13.8;7 Conclusions;321
13.9;8 Future Directions;322
13.10;References;322
14;42 Treatment of Staphylococcus aureus Infections;331
14.1;Abstract;331
14.2;1 Introduction;333
14.3;2 Guidelines for Therapy of S. aureus Infections;339
14.4;3 General Considerations for Therapy of S. aureus Infections;340
14.4.1;3.1 Noninvasive Skin and Soft Tissue Infections;340
14.4.2;3.2 Invasive Infections;347
14.5;4 Considerations in the Therapy of Specific Clinical Syndromes;349
14.5.1;4.1 Bacteremia;349
14.5.2;4.2 Endocarditis and Intravascular Infection;353
14.5.3;4.3 Pneumonia;354
14.5.4;4.4 Osteomyelitis, Including Discitis;356
14.5.5;4.5 Epidural Abscess;358
14.5.6;4.6 Septic Arthritis;359
14.5.7;4.7 Pyomyositis;360
14.5.8;4.8 Necrotizing Fasciitis;362
14.5.9;4.9 Impetigo;363
14.5.10;4.10 Mastitis and Breast Abscess;363
14.5.11;4.11 Conjunctivitis;364
14.5.12;4.12 Orbital Infections;364
14.5.13;4.13 Endophthalmitis and Panophthalmitis;365
14.5.14;4.14 Parotitis;366
14.5.15;4.15 Toxinoses;366
14.5.15.1;4.15.1 Staphylococcal Toxic Shock Syndrome (TSS);366
14.5.15.2;4.15.2 Staphylococcal Scalded Skin Syndrome (SSSS);367
14.5.16;4.16 Urogenital Infections;368
14.5.17;4.17 Lemierre’s Syndrome;369
14.5.18;4.18 Meningitis and Other CNS Infections;369
14.6;5 Conclusions;371
14.7;References;372
15;5004 The Innate Immune Response Against Staphylococcus aureus;390
15.1;Abstract;390
15.2;1 Introduction;391
15.3;2 The Encounter at the Epithelial Barrier;393
15.3.1;2.1 The Sentinel Function of Toll-like Receptor-2: Permitting Colonization and Preventing Invasion;394
15.3.2;2.2 Bacterial Invasion: Immune Defense Relies on Intracellular Sensors and Inflammasome Activation;396
15.3.3;2.3 Linking Inflammasomes to Protective T Cell Responses: The Role of NLRP3 in Th17 Differentiation;397
15.4;3 Professional Phagocytes and Their Effector Functions;398
15.4.1;3.1 Phagocytosis: Linking Intracellular Lysis to Antigen Presentation;398
15.4.2;3.2 Tissue-resident Phagocytes;400
15.4.2.1;3.2.1 Mast Cells: Well-prepared Guardians of Skin and Mucosa;400
15.4.2.2;3.2.2 Macrophages: Tissue-Specific Vigilants Balancing the Local Immune Response;400
15.4.3;3.3 Blood-Derived Phagocytes;401
15.4.3.1;3.3.1 Neutrophils: Recruited to Resolve Uncontrolled Spread of Infection;402
15.4.4;3.4 Dendritic Cells: Orchestrating the Adaptive Immune Response in Tissue and Lymph Nodes;403
15.4.4.1;3.4.1 Myeloid Dendritic Cells: Expert Control of T Cell Responses;403
15.4.4.2;3.4.2 Plasmacytoid Dendritic Cells and Type I Interferons: Fine-Tuning of Innate and Adaptive Immune Responses;404
15.5;4 The Last Frontiers Before Adaptive Immunity;405
15.5.1;4.1 Innate Immune B Cells: Rapid Supply of Antibacterial Antibodies;405
15.5.2;4.2 Natural Killer Cells: Neglected Sensors for Intracellular Persisting S. aureus?;406
15.5.3;4.3 Innate Lymphoid Cells: Confinement of S. aureus to Its Niche?;407
15.6;5 Conclusion;407
15.7;References;410
16;1 Adaptive Immunity Against Staphylococcus aureus;424
16.1;Abstract;424
16.2;1 Introduction;425
16.3;2 Immunological Overview;425
16.4;3 Role of B Cells and Antibodies;426
16.4.1;3.1 Preexisting Antibodies as Immunologic Correlates for Protection;427
16.4.2;3.2 Role of Antibodies in Vaccine-Mediated Protection;427
16.4.3;3.3 Evasion Mechanisms from the Humoral Immune Response;429
16.5;4 Role of T Cells;430
16.5.1;4.1 Th1 Cells;431
16.5.2;4.2 Th2 Cells;432
16.5.3;4.3 Th17 Cells;433
16.5.4;4.4 Regulatory T Cells;435
16.6;5 Conclusion;435
16.7;Acknowledgements;436
16.8;References;436
17;5017 Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation;445
17.1;Abstract;445
17.2;1 Introduction;447
17.3;2 The Mechanisms of Immune Evasion;448
17.4;3 Conserved Structural Properties of Evasion Molecules: A Structure–Function Analysis;451
17.4.1;3.1 Proteins Consisting of an OB-Fold and/or ?-Grasp Domain;453
17.4.1.1;3.1.1 The Superantigens;454
17.4.1.2;3.1.2 Superantigen-like Proteins;455
17.4.1.3;3.1.3 The EAP Domain Proteins;457
17.4.1.4;3.1.4 Chemotaxis Inhibitory Protein of S. aureus;457
17.4.1.5;3.1.5 FPR2 Inhibitory Proteins;458
17.4.1.6;3.1.6 Staphylokinase;458
17.4.1.7;3.1.7 Staphylococcal Nuclease;459
17.4.2;3.2 Proteins Consisting of a Triple Alpha Helix;459
17.4.2.1;3.2.1 The Immunoglobulin-Binding Proteins;459
17.4.2.2;3.2.2 The Staphylococcal Complement Inhibitor Family;460
17.4.2.3;3.2.3 The Extracellular Fibrinogen-Binding Protein Family;461
17.4.2.4;3.2.4 Staphylococcal Coagulases;461
17.4.3;3.3 The Staphylococcal Toxins: ?-Barrel Pore-Formers and ?-Helices;462
17.4.3.1;3.3.1 The ?-Barrel Pore-Forming Toxins;462
17.4.3.2;3.3.2 The Phenol-Soluble Modulins;464
17.4.4;3.4 Additional Secreted Enzymes;465
17.4.4.1;3.4.1 Staphylococcal Proteases;465
17.4.4.2;3.4.2 ?-Hemolysin;465
17.4.5;3.5 The Structure–Function Relationship;466
17.5;4 Genomic Location and Host Specificity;467
17.5.1;4.1 Core Variable Genome;468
17.5.1.1;4.1.1 Genomic Islands;468
17.5.1.2;4.1.2 Immune Evasion Cluster 2 (IEC2);471
17.5.1.3;4.1.3 Other Clustered Immune Evasion Genes;472
17.5.2;4.2 Mobile Genetic Elements;473
17.5.2.1;4.2.1 SaPIs;473
17.5.2.2;4.2.2 Prophages;474
17.5.3;4.3 Host Adaptation of Immune Evasion Molecules;476
17.6;5 Future Perspectives;477
17.6.1;5.1 Therapeutic Strategies Based on Evasion Molecules for S. aureus Infections;477
17.6.2;5.2 Therapeutic Strategies for Other Inflammatory Conditions and Cancer;479
17.7;6 Conclusions;480
17.8;Acknowledgements;480
17.9;References;481
18;54 Vaccines for Staphylococcus aureus and Target Populations;494
18.1;Abstract;494
18.2;1 Introduction;496
18.3;2 Rationale Behind the Need of a S. Aureus Vaccine;498
18.4;3 Target Populations Suitable for S. Aureus Vaccine Efficacy Trials;500
18.4.1;3.1 End-Stage Renal Disease (ESRD) Patients;500
18.4.2;3.2 Intensive Care Unit (ICU) Patients;508
18.4.3;3.3 Surgery Patients;508
18.4.4;3.4 Community-Acquired Skin and Soft Tissue Infections (CA-SSTIs) Patients;509
18.5;4 Preclinical Research on Antigens Selected for Clinical Development;511
18.5.1;4.1 Antigens that Reached Phase III Trials;511
18.5.2;4.2 Antigens Currently Being Tested in Phase II Trials;512
18.5.3;4.3 Antigen Combinations that Reached Phase I Trials;513
18.5.4;4.4 Recently Proposed Antigens that Are Still in Preclinical Phase;514
18.6;5 Clinical Data on Vaccine Candidates that Reached Phase III;516
18.6.1;5.1 Summary of Phase I–III Trial Data on V710;516
18.6.2;5.2 Summary of Phase I–III Trial Data on StaphVax;517
18.7;6 Lack of Established Correlates of Protection;519
18.8;7 Discussion;521
18.9;Acknowledgments;522
18.10;References;523
19;5005 Lysin Therapy for Staphylococcus aureus and Other Bacterial Pathogens;532
19.1;Abstract;532
19.2;1 Introduction;533
19.3;2 Mechanism of Action;534
19.4;3 Lysin Efficacy;536
19.5;4 Staphylococcus aureus-Specific Lysins;536
19.6;5 Synergy;537
19.7;6 Biofilms;538
19.8;7 Effects of Antibodies;538
19.9;8 Bacterial Resistance to Lysins;539
19.10;9 Conclusion;540
19.11;Acknowledgments;541
19.12;Literature Cited;541