Pathogenic Yeasts (eBook)

112284_1_En_FM1_OnlinePDF 1
112284_1_En_1_Chapter_OnlinePDF 9
1: Comparative Genomic Analysis of Pathogenic Yeasts and the Evolution of Virulence 9
Comparative Genome Analysis 11
Analysis of Basidiomycete Genomes 12
Analysis of Ascomycete Genomes 13
The Aspergilli 13
Candida Genomes 14
Evolution of Gene Families Associated with Virulence 15
Analysis of Synteny in Candida Genomes 17
Differential Gene Regulation and Evolution of Virulence 20
References 22
112284_1_En_2_Chapter_OnlinePDF 27
Chapter 2: Molecular Epidemiology of Candida Species 27
Introduction 27
Epidemiology of Candidosis 28
Molecular Epidemiology 30
DNA Fingerprinting with Dispersed, Repetitive Elements 30
Multi-Locus Sequence Typing (MLST) of C. albicans 32
Defining Clonal Clusters by MLST 35
Insights on Population Structure of C. albicans from MLST 35
Epidemiological Investigations with MLST 38
MLST of Non-C. albicans Candida Species 39
Future Directions for Typing of Candida Species 41
Conclusions 42
References 43
112284_1_En_3_Chapter_OnlinePDF 48
Chapter 3: Candida Infections and Modelling Disease 48
Candida Species as Commensals 48
Candida Species Associated with Disease 50
Oral Candidiasis 50
Vaginal Candidiasis 51
Disseminated Candidiasis 52
Modelling Candida Carriage and Infection 54
Experimental Models of Candida Infection: The Reductionist Approach 54
Cell-Based Models 54
Monocyte-Candida Interactions 54
Macrophage-Candida Interactions 55
Neutrophil-Candida Interactions 56
Dendritic Cell-Candida Interactions 56
Epithelial Cell- and Endothelial Cell-Candida Interactions 57
Reconstituted Human Epithelial Models (RHE) and Tissue Explants 57
Whole Animal Approaches 58
Invertebrate Models 58
Vertebrate Models 58
Mucosal Models 59
Models of Oral and Gastrointestinal Carriage and Infection 59
Models of Vaginal Carriage and Infection 60
Models of Systemic Infection 61
Gastrointestinal Dissemination 61
Intravenous Challenge 61
References 62
112284_1_En_4_Chapter_OnlinePDF 75
Chapter 4: Candida albicans Cell Wall Mediated Virulence 75
C. albicans Cell Wall Architecture 75
Cell Wall Proteins 76
Cell Wall Remodelling During Morphogenesis and Variation in pH 78
Phenotypic Switching 81
Comparative Cell Wall-Omics 81
Glycosylphosphatidylinositol Anchored Cell Wall Proteins 82
Cell Wall Associated Virulence Attributes 82
Adhesion 82
Als family 83
Eap1 84
Hwp1 84
Ywp1 84
Int1 85
Cell Surface Hydrophobicity 85
Superoxide Dismutases (SODs) 86
Phospholipases 86
Iron Binding Proteins 87
Als3 a Multi-Functional Adhesin, Invasin and Ferritin-Binding Protein 87
Biofilm Formation 88
Interactions with Host Cells 89
Wall as Potential Source of Novel Therapies 90
Future Perspectives 90
References 91
112284_1_En_5_Chapter_OnlinePDF 102
Chapter 5: Secreted Candida Proteins: Pathogenicitypathogenicity and Host Immunity 102
Introduction 102
The Secretory Pathwaysecretory pathway in Fungi 103
The Secretory Proteins of Candida spp. 104
Non-Covalently Linked Cell Wall Associated Secreted Proteins 104
Candida Proteins Secreted from the Cell 107
Candida Secreted Aspartyl Proteinases 107
Candida Secreted Aspartyl Proteinases: Processing, Activation and Structuresecreted aspartyl proteinasesprocessing, activation 108
Candida Secreted Aspartyl Proteinases: Role in Pathogenicitysecreted aspartyl proteinasesrole in pathogenicity 109
Candida Secreted Phospholipases 113
Candida Phospholipases: Role in Pathogenicityphospholipasesrole in pathogenicity 114
Candida-Secreted Lipases 114
Candida Lipases: Role in Pathogenicitylipasesrole in pathogenicity 115
Other Secreted Enzymes 115
The Candida Proteomeproteome and secretomesecretome 116
The Host Responsehost response to Candida Secreted Proteins 116
Conclusion 118
References 118
112284_1_En_6_Chapter_OnlinePDF 126
Chapter 6: Yeast Biofilms 126
Introduction 126
Clinical Significance 127
What are Biofilms? 128
Fungal Biofilm Model Systems 129
Biofilm Developmental Characteristics 131
Molecular Mechanisms of Biofilm Development 134
Pathogenesis and Host Immunity 137
Antifungal Resistance 138
Cell-Cell Communication 140
Conclusions 141
References 142
112284_1_En_7_Chapter_OnlinePDF 150
Chapter 7: Cryptococcus: Spectrum of Disease and Treatment 150
Introduction 150
Clinical Presentations 151
Risk Factors: Immunosuppressed v Immunocompetent 151
C. neoformans v C. gattii 152
Central Nervous System (CNS) 152
Lung 153
Other Organs 153
Laboratory Diagnosis 154
Microscopy 154
Serology 154
Culture and Sensitivity 155
Treatment 155
Antifungal Therapy 156
Cryptococcal Meningoencephalitis/Disseminated Disease 156
HIV-Infected Patients 156
Organ Transplant Recipients 158
Immunocompetent Patients 158
Cerebral Cryptococcomas 158
Pulmonary Disease 159
Isolated Cryptococcal Antigenaemia and Screening for Subclinical Infection 159
Management of Complications 159
Raised Intracranial Pressure 159
Relapse 160
Immune Reconstitution Inflammatory Syndrome (IRIS) 160
Restoration and Boosting of Host Immunity 161
Prognostic Factors and Outcome 162
References 162
112284_1_En_8_Chapter_OnlinePDF 171
Chapter 8: Typing Species of Cryptococcus and Epidemiology of Cryptococcosis 171
Introduction 171
Molecular Methods 172
Molecular Markers 173
Randomly Amplified Polymorphic DNA (RAPD) 174
PCR Fingerprinting 175
Microsatellites 175
Amplified Fragment Length Polymorphisms (AFLP) 176
PCR-Restriction Fragment Length Polymorphism (RFLP) 176
DNA-DNA Hybridization 177
DNA Sequencing 177
Method Selection 178
Applications of Molecular Typing 178
Identification 179
Pathogenesis and Phenotypic Strain Variation 180
Elucidate the Epidemiology and Ecology of Cryptococcus Species 181
Population Genetics of Cryptococcus 182
Ecology and Epidemiology of Cryptococcosis 182
C. neoformans 183
C. gattii 184
Conclusions 185
References 186
112284_1_En_9_Chapter_OnlinePDF 195
Chapter 9: Environmental Stress-Sensing and Pathogenicity in Cryptococcus neoformans 195
Introduction 195
The Main Phenotypes Elaborating C. neoformans Stress Responses 195
Capsule Enlargement 196
Biofilm Formation 196
Melanin Formation 197
The Genes Involved in the C. neoformans Stress Responses 197
Oxidative and Nitrosative Stress Responses 197
Superoxide Dismutases 198
Glutathione Peroxidases 198
Thiol Peroxidase 199
Thioredoxin 199
Laccase 199
Alternative Oxidases 200
Flavohemoglobin Denitrosylase 200
High Temperature Resistance 201
Trehalose (a-glucopyranosyl-a-d-glucopyranoside) 201
Cyclophilin A 201
Iron Deprivation 202
Calcium Deprivation 202
Stress-Sensing and -Signaling Pathways in C. neoformans 203
Calmodulin/Calcineurin Calcium Mediated Signaling 203
The Hog1p MAPK Pathway 204
The PKC1 MAPK Signaling Pathway 205
The cAMP Signaling Pathway 206
The Main Transcription Factors Involved in the C. neoformans Stress Responses 206
Nrg1p 207
Atf1p and Yap4p 207
Skn1p 207
Ssa1p 208
Cir1p 208
Conclusion 208
References 209
112284_1_En_10_Chapter_OnlinePDF 213
Chapter 10: Malassezia 213
Introduction 213
Taxonomy of Malassezia 214
Physiology and Biochemistry 215
Cell Structure 215
Dimorphism 215
Lipid Dependence and Culture Requirements 216
Metabolite Production 216
Commensalism 217
Role in Disease 218
Pityriasis Versicolor 219
Seborrhoeic Dermatitis and Dandruff 221
Atopic Eczema 222
Other Cutaneous Diseases 225
Systemic Diseases 226
Summary and Conclusions 226
References 227
112284_1_En_11_Chapter_OnlinePDF 235
Chapter 11: Emerging Systemic Yeast Pathogens 235
Introduction 235
Non-albicans Candida 236
Microbiology 236
Epidemiology 236
Clinical Manifestations 237
Diagnosis 237
Antifungal Susceptibility, Therapy and Outcome 237
Trichosporon Species 238
Microbiology 238
Epidemiology 238
Clinical Manifestations 239
Diagnosis 239
Antifungal Susceptibility, Therapy and Outcome 239
Rhodotorula 240
Microbiology 240
Epidemiology 240
Clinical Manifestations 241
Diagnosis 241
Antifungal Susceptibility, Therapy and Outcome 241
Blastoschizomyces capitatus 241
Microbiology 241
Epidemiology 242
Clinical Manifestations 242
Diagnosis 242
Antifungal Susceptibility, Therapy and Outcome 243
Saccharomyces 243
Microbiology 243
Epidemiology 243
Clinical Manifestations 244
Diagnosis 244
Antifungal Susceptibility, Therapy and Outcome 244
Malassezia 245
Microbiology 245
Epidemiology 245
Clinical Manifestations 245
Diagnosis 246
Antifungal Susceptibility, Therapy and Outcome 247
Pichia Species 247
Microbiology 247
Epidemiology 247
Clinical Manifestations 248
Diagnosis 248
Antifungal Susceptibility, Therapy and Outcome 248
Conclusions 249
References 249
112284_1_En_12_Chapter_OnlinePDF 256
Chapter 12: Yeast Pathogens of Domestic Animals 256
Introduction 256
Candida 257
Cat and Dog 259
Cattle 260
Bovine Abortion 260
Bovine Mastitis 260
Horse 261
Poultry 262
Swine 263
Cryptococcus 265
Cryptococcus neoformans 266
Cryptococcus gattii 268
Malassezia 270
Malassezia pachydermatis 270
Lipid-dependent Species 273
Concluding Remarks 275
References 276
112284_1_En_13_Chapter_OnlinePDF 283
Chapter 13: Laboratory Diagnosis of Yeast Infections 283
Introduction 283
Direct Microscopy 284
Direct Microscopy of Unfixed Specimens 284
Histopathological Examination 286
Blood Culture Systems 286
Culture Media 288
Methods for Identification of Yeasts 289
The Germ Tube Test 289
Chlamydospores, Hyphae and Pseudohyphae 291
Capsule Formation 292
Structures Associated with Sexual Reproduction in Yeasts 292
Assimilation and Fermentation in Yeasts 293
Other Physiological Tests 293
Enzyme-Based Yeast Identification Systems 295
Commercial Yeast Assimilation Panels 296
Immunological Identification of Yeast Isolates 297
Molecular Identification of Yeast Isolates 297
Peptide Nucleic Acids 300
Algorithms for Identification 301
Non-Culture-Based Methods of Laboratory Diagnosis 301
The Future of the Diagnosis of Yeast Infections 302
References 303
112284_1_En_14_Chapter_OnlinePDF 312
Chapter 14: Antifungal Susceptibility Testing and Therapy 312
Antifungal Susceptibility Testing 312
An Update on the AST Standardization Process 312
Commercial Methods for AST of Yeasts 315
Epidemiology of Resistance of Yeasts In Vitro 316
Therapy of Yeast Infections 318
Therapy of Candida Infections 318
Therapy of Infections due to Cryptococcus 322
Therapy of Other Yeast Infections 323
References 323
112284_1_En_15_Chapter_OnlinePDF 328
15: Mechanisms of Multidrug Resistance in Fungal Pathogens 328
Introduction 328
Resistance Mechanisms Mediated by Antifungal Efflux: Azoles as an Exemplary Case 332
Upregulation of Membrane Efflux Transporters 333
Efflux Mediated by ABC Transporters 334
Efflux Mediated by MFS Transporters 337
Factors Modifying the Activity of Multidrug Transporters 339
Plasma Membrane Composition and Impact on Transporter Functions 339
Posttranslational Modifications 339
Molecular Mechanisms of Multidrug Transporter Regulation 340
Experimental Approaches for the Identification of cis- and trans-Elements Regulating Multidrug Transporters Expression 340
Model Systems and Their Application to Fungal Pathogen Research 340
Systematic Analysis of cis-Acting elements in the Promoters of Multidrug Transporters 342
Transcriptional Profiling for Regulator Identification 343
Coactivators in the Regulation of Multidrug Resistance Genes 344
Conservation of Multidrug Resistance Regulators in Pathogenic Fungi 345
Gain-of-Function Mutations in Transcription Factors Regulating Efflux Genes 346
Chromosomal Rearrangements Affecting Multidrug Transporter Expression 349
Strategies to Combat Multidrug Resistance in Yeast 350
Conclusion 350
References 351
: Index 360