Human Fungal Pathogens

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Index

A Anidulafungin ABC1, 188 candidiasis management, 340 ABPA. See Allergic bronchopulmonary aspergillosis structure, 273 Acanthamoeba castellanii,10 Antibody directed cell toxicity, 108 Ace2, 69 Antibody therapy. See Immunotherapy Acrophialophora, 520 Antifungals. See Drug development; specific drugs Acrophialophora fusispora, 520 APECED, 105, 150–151 AD. See Atopic dermatitis App1, 185 AD-HIES. See Autosomal dominant APR1, 239 hyper-immunoglobulin E syndrome ARG4,68–69 Adenylate kinase, lysis assay for drug development, 277 Armellaria mellea,26 ADH5, 172 Ascomycetes, 196 Adh5, 371 Ascomycota, 4–8, 11–14, 23–25, 33, 120 AFR1, 370 Ashbya gossypii, 196 Afr1, 367 Aspergillosis. See Allergic bronchopulmonary AIDS. See HIV/AIDS aspergillosis; Invasive aspergillosis AIF1,84 Aspergillus Allergic bronchopulmonary aspergillosis (ABPA), 439 evolution, 24, 27, 31 Als3, 168–169, 202, 220–223, 245, 293, 417–418 overview, 12–14 ALS proteins, 164–165 Aspergillus flavus, 52, 435–436 Alternaria, 14, 521–522 Aspergillus fumigatus Alternaria alternata, 124, 519, 521–522 amino acid metabolism, 240 Alternaria chlamydospora, 521–522 aspergillosis. See Invasive aspergillosis Alternaria dianthicola, 521 B-cell immunity, 107–108 Alternaria infectoria, 521–522 biofilm, 162, 170, 173–174 Alternaria longpipes, 521 carbon assimilation, 240, 243 Alternaria tennissima, 521 cell invasion Amphotericin B adherence mechanisms, 224–225 adverse effects, 328 molecular mechanisms, 224 biofilms in resistance, 173–174 overview, 223–224 candidiasis management, 339–340, 352 clinical trials Cryptococcus treatment, 342–345, 350–351 overview, 354–355 endemic fungi infection management, 357 prospects, 355 entomophthoramycosis management, 506–507 dendritic cell invasive aspergillosis management, 355 immunotherapy, 290 mechanism of action, 272 response, 94, 97 mucormycosis management, 487–488 diagnosis, 265 pharmacodynamics of lipid formulations, 307–308 drug resistance, 368 structure, 273 ecology, 433 AN2690, 279–280 evolution, 24, 26–29, 32 Aneuploidy. See also Ploidy change innate immunity, 121–122, 124, 126–127 consequences, 83–85 iron metabolism, 246 loss of heterozygosity, 84–85 laboratory identification and biology, 433–436 mechanisms in generation, 81–83 macrophage engulfment, survival, and replication, overview, 80–81 184–185 Anhidrotic ectodermal dysplasia with overview, 12–13 immunodeficiency (EDA-IE), 153 pattern recognition receptors, 100

563

Aspergillus fumigatus (Continued) Basidomycota, 14 ploidy change, 75–77 Batrachochytrichium,25 section Fumigati, 432–433 B cell, pathogen response, 107–108 sexual reproduction BCR1, 165, 168 drug resistance role, 53 Bcr1, 167, 169, 420 other Aspergillus species, 521 Bcy1, 203 overview, 51 Bgl2, 172 pathogen population biology significance, Biatriospora, 522 52–53 Biatriospora mackinonii, 522 sexual cycle, 51–52 Bin1, 207 T-cell immunity, 107 Biofilm vaccination, 291 comparative genomics, 168–169 zinc assimilation, 247 drug resistance Aspergillus lentulus,52–53 azoles, 371 Aspergillus nidulans echinocandins, 374 aspergillosis. See Invasive aspergillosis extracellular matrix chronic granulomatous disease, 146 Candida laboratory identification and biology, 433–436 drug resistance role, 170–171 morphogenesis, 195, 198 eDNA in drug resistance, 173 ploidy change, 76–78 glucan production, 171–172 Aspergillus niger, 52, 434–436 production, 169–170 Aspergillus oryzae, 197 Aspergillus drug resistance, 173–174 Aspergillus terreus, 52, 434–435 genetic control of development, 162, 164–168 Aspf2, 247 multispecies biofilms, 168 Ato5, 238 prospects for study, 174 Atopic dermatitis (AD), Malassezia role, 475–476 rationale for study, 161–162 Atx1, 397 species and clinical significance, 163–164 Aureobasidium, 522 Bipolaris, 14, 522 Autosomal dominant hyper-immunoglobulin Bipolaris australiensis, 522 E syndrome (AD-HIES), 148–149 Bipolaris hawaiiensis, 519, 522 Autosomal recessive hyper-immunoglobulin Bipolaris spicifera, 522 E syndrome, 153 Black fungi Axl2, 198 Acrophialophora, 520 Alternaria, 520–522 antifungal therapy, 530–531 B Aureobasidium, 522 Backusella circina, 494 Biatriospora, 522 Bad1, 228 Bipolaris, 522 Basidiobolus Chaetomium, 523 clinical features, 502–503 Chladophialophora, 523 diagnosis, 505–506 clinical spectrum of diseases, 518–521 ecology, 496–497 Curvularia, 523 epidemiology, 496–497 Cyphellophora, 523–524 evolution, 25 diagnosis, 529–530 life cycle, 499 Exophiala, 524–525 management, 506–507 Exserohilum, 525 overview, 5–4, 494–495 Falciformispora, 525 pathogenesis, 502 Fonsecaea, 525–526 taxonomy, 495–498 Hortaea, 526 Basidiobolus heterosporus, 497 Knufia, 526 Basidiobolus lacerate, 497 Madurella, 526 Basidiobolus meristosporus, 497 Medicopsis, 526 Basidiobolus microspores, 497 Neoscytalidium, 526–527 Basidiobolus ranarum, 4, 496–497, 488.503, 506–507 Ochoconis, 527 Basidiomycetes, 196–197 overview, 517–518 Basidiomycota, 8–11, 25–26, 120 Phaeoacremonium, 527

564

Phialophora, 527 drug resistance, 367–368, 370–371 Phoma, 527–528 epidemiology, 413–414 Pseudochaetosphaeronema, 528 evolution, 26–28, 30–33 Pyrenochaeta, 528 genome profiling Rhinocladiella, 528 gene-deletion methods, 68–69 Trematosphaeria, 528–529 homozygous knockouts, 69 Veronaea, 529 industry collections, 69–70 Verruconis, 529 resources, 65 Blastomyces, 4–5, 24, 27 transcription factor knockouts, 69 Blastomyces dermatitidis genome studies, 416–419 cell invasion, 228 innate immunity, 121–122, 124–126, 129 diagnosis, 266 iron metabolism, 245–246 epidemiology, 452 life cycle and genome, 67–68 evolution, 26 macrophage engulfment, survival, and replication, morphogenesis, 201, 205 180–184 T-cell immunity, 102, 107 morphogenesis, 200–209 thermal dimorphism, 452–453 nitrogen assimilation, 237–240 vaccination, 292 overview, 11–12 Bni1, 199 parasexual reproduction, 47–51 Brg1, 204 pattern recognition receptors, 100–102 Bud1, 198 ploidy change, 74–75, 77–79 Bud3, 198 vaccination, 291, 294 Bud4, 198 zinc assimilation, 247 Bud8, 198 Candida dubliniensis Bud9, 198 evolution, 26, 31 genome studies, 418–419 Candida glabrata C carbon assimilation, 240 CalA, 224 drug resistance, 370–371 CAN1, 239 epidemiology, 413–414 CAN2, 399 evolution, 33 Candida genome studies, 420–422 evolution, 24, 28, 30–31 iron metabolism, 245–246 overview, 11–12 macrophage engulfment, survival, and replication, pathogens, 413–414 180–184 taxonomy, 413–416 nitrogen assimilation, 237, 239 treatment principles. See Candida treatment overview, 11 principles zinc assimilation, 247 vaginosis mycobiome, 560 Candida guillermondii, 420 Candida albicans Candida krusei aneuploidy, 80, 82, 85 epidemiology, 413–414 B-cell immunity, 107–108 overview, 11 biofilm Candida lusitaniae, 1, 420, 77, 82 comparative genomics, 168–169 Candida metapsilosis,28 drug development, 276 Candida orthopsilosis,28 extracellular matrix Candida parapsilosis drug resistance role, 170–171 biofilms 166, 168–169 eDNA in drug resistance, 173 cell invasion, 223 glucan production, 171–172 epidemiology, 413–414 production, 169–170 evolution 28 genetic control of development, 162, 164–168 genome studies, 419–420 multispecies biofilms, 168 nitrogen assimilation, 237 carbon assimilation, 240–244 overview 11 cell invasion Candida treatment principles endothelial cell, 122–123 antifungal agents and spectrum of activity, 340 epithelial cell, 119–122 clearance confirmation, 339

565

Candida treatment principles (Continued) CDR2, 367–368, 370 clinical trials CDR3, 367 overview, 352–353 CDR4, 367 prospects, 353 CDR11, 367 disseminated infection CFEM proteins, 164, 169, 173 bone, 341 Cfl1, 209, 225 central nervous system, 341 CfmA, 224 endocardium, 341 CfmC, 224 eye, 339 Cfo1, 246, 399 renal tract, 339, 341 Cft1, 246 drug resistance. See Drug resistance CGD. See Chronic granulomatous disease general treatment principles. See Treatment Chaetomium, 523 principles, mold infection Chaetomium atrobrunneum, 523 meningioencephalitis in HIV, 339 Chaetomium funicola, 523 overview, 337–338 Chaetomium globusum, 523 rapid and effective antifungal therapy, 338 Chaetomium perlucidum, 523 source removal, 338 Chaetomium strumarium, 523 therapy modification according to species Chitin synthase, drug resistance, 374–376 determination and susceptibility Chladophialophora, 523 testing, 338 Chladophialophora arxii, 523 Candida tropicalis Chladophialophora bantiana, 523 epidemiology, 413–414 Chladophialophora boppii, 523 evolution, 28 Chladophialophora carrionni, 523 genome studies, 77, 419–420 Chladophialophora devriesii, 523 overview, 11 Chladophialophora emmonsii, 523 Cap1p, 183 Chladophialophora saturnica, 523 Carbon assimilation Chromoblastomycosis, 518 central carbon metabolism Chronic granulomatous disease (CGD), regulation in host niches, 242–243 fungal infection susceptibility, 141, regulatory rewiring, 241–242 146, 439 overview, 240–241 Chs2, 375 virulence factor impact, 243–244 Chs8, 375 CARD9, signaling defects and fungal infection Cir1, 247, 399 susceptibility, 152–153 Cla4, 199 Caspase-1, 129 Cladophialphora bantianum,14 Caspofungin Clinical trials. See Drug development candidiasis management, 340 Cln1, 207 mechanism of action, 274 Clostridium difficile diarrhea, mycobiome, structure, 273 558–560 CatB, 188 CLR. See C-type lectin CatP, 188 CMV. See Cytomegalovirus Cbp1, 202, 455 CNA1, 397 Ccc1, 247 Cnc1560, 197 Ccc2, 397 CnPlb1, 186 Cch1, 206 Coccidiodes, 4–5, 7, 24, 27, 31–32 CD11b, 224 Coccidiodes immitis CD18, 224 evolution, 23, 26–29, 31–32 CD44, 226–227 host defense, 487 Cdc3, 200 innate immunity, 127 Cdc10, 200 macrophage engulfment, survival, and replication, Cdc11, 200 186–187 Cdc12, 200 morphogenesis, 201 Cdc35, 208 overview, 4 Cdc42, 194–195, 198–200, 206 T-cell immunity, 102 Cdk1, 206 thermal dimorphism, 453–454 CDR1, 367–369, 372–373 vaccination, 291

566

Coccidiodes posadasii life cycle, 391–392 evolution, 27, 31–32 macrophage engulfment, survival, and replication, macrophage engulfment, survival, and replication, 185–186 186–187 overview, 8–10, 25, 28, 42, 44–46 overview, 4 stress response and signaling, 400–402 thermal dimorphism, 453–454 virulence factors vaccination, 291 capsule Comparative genomics, fungus evolution, 30–32 melanization, 397 Complement fixation, diagnostics, 259 regulation of formation and secretion, Complement receptor 3 (CR3), 128 396–397 Conidiobolus structure and synthesis, 394–395 clinical features, 502–505 degradation enzymes, 398–399 diagnosis, 505–506 growth at body temperature, 397–398 ecology, 496–497 Cryptococcus neoformans epidemiology, 496–497 aneuploidy, 81, 83–84, 86 life cycle, 499–501 antibody therapy, 287–289 management, 506–507 B-cell immunity, 107–108 overview, 3–4, 494–495 biofilm, 174 pathogenesis, 502 carbon assimilation, 242–243 taxonomy, 495–496, 498, 500–501 cell invasion, 225–227 Conidiobolus brefeldianus, 496 Cryptococcus gattii comparison Conidiobolus coronatus, 4, 496, 500–501, 503–504, 507 genotype, 393–394 Conidiobolus firmipelleus, 496 phenotype, 393 Conidiobolus incongruus, 4, 496, 501, 505 diagnosis, 264–265 Conidiobolus lampragues, 496, 500, 504–505 drug resistance, 367, 391 Conidiobolus minor, 498 ecology, 387–388 Conidiobolus osmodes, 496 environmental sensing and response, 399–400 Conidiobolus pumilus, 496 epidemiology of infection, 388–389 Conidiobolus rhysosporus, 496 evolution, 25, 27–29, 32–33 Conidiobolus thromboides, 496 genome profiling Conidiobolus utriculosis, 498 capsule-independent phagocytosis inhibition, 66 Contact sensing, hyphal morphogenesis, 206 cross-species genetic interaction mapping, 67 Copper, transport, 247 gene-deletion methods, 65–66 CotH2, 228 resources, 65 CotH3, 228 SREBP pathway in virulence, 66–67 CpcA, 240, 248 systematic genetic analysis of virulence, 66 CPS1, 227 history of study, 385–386 CR3. See Complement receptor 3 host defense, 487 CRAG test, 344 immune response and pathogenesis, 389–390 CrAg LFA, diagnostics, 265–267 innate immunity, 121–122 Cryptococcus iron metabolism, 246–247 evolution, 24–25, 30 life cycle, 64, 391–392 overview, 8–11 macrophage engulfment, survival, and replication, treatment principles. See Cryptococcus treatment 182, 185–186 principles morphogenesis, 196–197, 205, 208 Cryptococcus gattii overview, 8–10 aneuploidy, 81 ploidy change, 74–76, 79–80 Cryptococcus neoformans comparison sexual reproduction, a-a opposite sex bisexual genotype, 393–394 reproduction phenotype, 393 genetic hybrid studies, 44 diagnosis, 266 monokaryotic fruiting, 43 ecology, 387–388 overview, 42 environmental sensing and response, 399–400 population genetics studies, 45–47 epidemiology of infection, 389 unisexual reproduction, 43–44 history of study, 386 virulence links, 47 immune response and pathogenesis, 389–390 stress response and signaling, 400–402

567

Cryptococcus neoformans (Continued) D T-cell immunity, 104–105, 128 taxonomy and nomenclature, 386–387 Dandruff, Malassezia role, 475 vaccination, 292 DC. See Dendritic cell virulence factors DC-SIGN, innate immunity, 128 capsule Dectin-1 melanization, 397 CARD9 signaling defects and fungal infection regulation of formation and secretion, susceptibility, 152–153 396–397 gut inflammation role, 559–560 structure and synthesis, 394–395 pathogen recognition, 100, 105, 126–127, degradation enzymes, 398–399 179–180, 290 growth at body temperature, 397–398 Dectin-2, pathogen recognition, 100–101, 127 Cryptococcus neoformans var. grubii, 9–10, 28, 394 Dectin-3, pathogen recognition, 101 Cryptococcus treatment principles Deferasirox, mucormycosis management, 488 clinical trials Deferoxamine, mucormycosis risks, 485 overview, 350–351 Dendritic cell (DC) prospects, 351–352 conventional dendritic cells, 94, 96 complications contributing to persistent or relapsed functional overview, 94–95, 122 infection, 344–345 immunotherapy, 289–290 CRAG screening and preemptive treatment, 344 intestine, 97 drug resistance. See Drug resistance lung, 97 general treatment principles. See Treatment migratory dendritic cells, 96 principles, mold infection monocyte-derived dendritic cells, 97–98 immunity restoration and inflammation plasmacytoid dendritic cells, 94 management, 343–344 skin, 96 intracranial pressure elevation management, 343 vaccination, 290 meningioencephalitis in HIV, 342–343 Dermatophytes overview, 341–342 genera, 467 rapid and effective antifungal therapy, 342–343 genome features and analysis, 469, 472–474 risk stratification, 342 mycobiome analysis of skin, 469–470 toxicity minimization, 343 overview, 470 C-type lectin (CLR), overview, 98–100 phylogenetic relationships, 468 CSH1, 172, 371 skin diseases CSMA, 376 overview, 467–469 CSMB, 376 species and epidemiology, 471–472 CSP1, 419 treatment, 472 CSP2, 419 Diabetes, mucormycosis risks, 485 CspA, 224 Diagnosis, fungal infection Csy1, 239 antigen detection Cta1p, 183 advantage sand limitations, 266 Ctr1, 247 cryptococcosis, 264–265 Curvularia, 14, 523 galactomannan, 265–266 Curvularia aeria, 523 pan-fungal detection of b-glucan, 266 Curvularia brachyspora, 523 black fungi, 529–530 Curvularia clavata, 523 entomophthoramycosis, 505–506 Curvularia geniculata, 523 molecular diagnostics Curvularia inaequalis, 523 challenges, 263–264 Curvularia lunata, 519, 523 culture-based methods, 260–262 Curvularia pallescens, 523 non-culture-based methods, 258–260 Curvularia verruculosa, 523 proteomics, 262–263 Cyclosporine A, 489 overview, 257–258 CYP51A. See Ergl1 prospects, 255–267 Cyphellophora, 523–524 sample collection, 258 Cyphellophora pluriseptata, 520 serology, 258–259 Cyr1, 202–203, 205–206, 208 Dimorphism. See Thermally dimorphic fungi Cytomegalovirus (CMV), 330 DLH1,79

568

DOCK8, deficiency and fungal infection susceptibility, DTRK3, 226 153 Dur31, 238, 367 Drug development. See also specific drugs Dutch elm disease, 201 challenges, 275 clinical needs, 274–275 clinical trials E candidiasis E1210, 279 overview, 352–353 Eap1, 168 prospects, 353 EC. See Epithelial cell cryptococcosis Echinocandin, structure, 273 overview, 350–351 EDA-IE. See Anhidrotic ectodermal dysplasia with prospects, 351–352 immunodeficiency endemic fungi infection, 356–358 eDNA, biofilms and eDNA in drug resistance, 173 invasive aspergillosis Eed1, 207 overview, 354–355 EFG1, 420–421 prospects, 355 Efg1, 169, 203, 207–208, 244, 420 historical perspective, 274 Ena1, 402 infection classification, 272 Endothelial cell, Candida invasion, 122–123 overview of current therapies, 272–274 ENO1, 242 pharmacodynamics. See Pharmacodynamics, Entomophthoromycota. See also Basidiobolus; antifungals Conidiobolus pharmacokinetics. See Pharmacokinetics, ecology, 496–497 antifungals epidemiology, 496–497 process and new approaches, 275–278 life cycle, 499 prospects, 281 overview, 3–4, 494–495 targets and molecular scaffolds, 278–280 taxonomy, 495–498, 500 Drug resistance. See also specific drugs and organisms Enumafungin, 279 Aspergillus sexual reproduction role, 53 Enzyme immunoassay, diagnostics, 259 biofilm extracellular matrix EPA genes, 420–421 Aspergillus drug resistance, 173–174 Epidermophyton,8 Candida Epithelial cell (EC) drug resistance role, 170–171 Candida invasion, 119–122 eDNA in drug resistance, 173 innate immunity, 123 mechanisms ERG11, 83, 85 assessment, 364–365 ERG25, 400 azoles Erg3, 367, 372 biofilms, 371 Ergl1, 277, 280, 364, 366–367, 370–371, 377, 391, 492 chromosomal abnormalities, 370 Exophiala, 24, 524–525 efflux, 367–368 Exophiala dermatitidis, 14, 525 Ergl1 substitutions and alterations, 364, Exophiala oligosperma, 525 366–367 Exophiala spinifera, 525 Hsp90, 372 Exophiala xenobiotica, 525 MDR expression regulation, 368–370 Exserohilum, 525 messenger RNA stability, 372–373 Exserohilum longirostratum, 525 mitochondrial defects, 370–372 Exserohilum mcginnisii, 525 multiple mechanisms, 371 Exserohilum rostratum, 525 uptake, 367 echinocandins adaptive cellular factors, 374 F biofilms, 374 Falciformispora, 525 cell integrity circuit, 376–377 Falciformispora senegalensis, 525 chitin synthase, 374–376 Falciformispora tompkinsii, 525 FKS substitutions and polymorphisms, Fbp1, 241 373–374 FCA1, 367 Hsp90, 376 FCY2, 367 prospects for study, 377 FCY22, 367

569

FCY23, 367 GCN4, 240 Ferricrocin, 246 Gcn4, 244, 248 Fet3, 246 Gcr1, 241 FK506, mucormycosis management, 489–490 Gcr2, 241 FKS, substitutions and polymorphisms in drug Genito-urinary tract, innate immunity, 124 resistance, 373–374 Ggt1, 246 FKS1, 171–172, 373–374.376, 420 Gic1, 199 FKS2, 373, 376, 420 Gic2, 199 Flo8, 203 Glucan synthesis, therapeutic targeting, 274, 277–278, Fluconazole 280, 364, 488 candidiasis management, 338–341, 352 Glucuronoxylomannan, diagnostics, 264 combination therapy, 277–278 Glycosylphosphatidylinositol (GPI), therapeutic Cryptococcus treatment, 342, 351 targeting, 278–279 endemic fungi infection management, 357 Gpa2, 203 mechanism of action, 273, 277 GPI. See Glycosylphosphatidylinositol pharmacodyanamics, 310 Gpr1, 203 structure, 273 GRACE, 70 Flucytosine GRP78, 228, 486–487 black fungus management, 530 GWT1, 279–280 candidiasis management, 341, 351 clinical implications, 309 concentration effect, pharmacodynamic index, and H target, 308–309 Hap3, 247 Cryptococcus treatment, 342 Hap5, 247 uptake, 367 Haploinsufﬁciency proﬁling (HOP), 281 5-Fluorocytosine. See Flucytosine HapX, 246–247 Folliculitis, Malassezia role, 477 Hda1, 204, 207 Fonsecaea, 525–526 Heat intolerance, pathogenic fungi, 2 Fonsecaea monophora, 525 Hematopoietic stem cell transplantation (HSCT), Fonsecaea pedrosoi, 525 invasive aspergillosis, 440 Fonsecaea rubrica, 525 HER2, 221 FsC, 246 Herpotrichiellaceae, 518–519, 523 Ftr1, 246 Heterobasidion annosum,26 Fusarium, 14, 31 High osmolarity glycerol response (HOG), 400–401 Fusarium oxysporum,14 Histoplasma, 4–6, 24, 31 Fusarium solanum,14 Histoplasma capsulatum amino acid metabolism, 240 antibody therapy, 287 G B-cell immunity, 107–109 GAL1, 241 dendritic cell response, 94, 96 Gal4, 241 diagnosis, 259, 265–266 GAL7, 241 evolution, 27, 31 GAL10, 241 innate immunity, 130 Galactomannan, diagnostics, 265–266 iron metabolism, 246 Galactosaminogalactan, 224–225 macrophage engulfment, survival, and replication, GAP1, 239 187–188 Gap1, 197 morphogenesis, 201–202, 205 GAP2, 239 overview, 4–7 Gastrointestinal tract, innate immunity, 124 pattern recognition receptors, 100–101 Gat1, 247 T-cell immunity, 102–107 Gat201, 66, 185 thermal dimorphism, 454–456 Gat204, 66, 185 HIV/AIDS GATA2, mutations and fungal infection cryptococcal menigioencephalitis treatment, 339, 342 susceptibility, 150 Cryptococcus infection, 47, 185, 265, 285, 292, 342, GCA1, 172 344, 350–352, 357, 388, 420 GCA2, 172 mucormycosis, 485

570

opportunistic infection trends, 272, 285, 351 Dectin-1–CARD9 signaling defects, 152–153 oral mycobiome, 556–557 DOCK8 deficiency, 153 Paracoccidiodes brasiliensis infection, 456 GATA2 mutations, 150 Pneumocystis pneumonia. See Pneumocystis interferon regulatory factor 8 mutations, 151–152 pneumonia myeloperoxidase deficiency, 146–147 transmission, 15 overview of primary immunodeficiencies, 139–145 vaccination, 292 prospects for study, 154–155 HOG. See High osmolarity glycerol response STAT1 mutations, 149–150 Hog1, 182, 204, 402 STAT3 mutations, 148–149 Holleya sinecauda, 201 STK4/MST1 mutation, 154 HOP. See Haploinsufficiency profiling TYK2 deficiency, 153 HOP1,79 Inflammasome, innate immunity, 129–130 Hortaea, 526 Inflammatory bowel disease, mycobiome, 558–560 Hortaea werneckii, 526 InlA, 221 HSCT. See Hematopoietic stem cell transplantation Innate lymphoid cell (ILC), functional overview, Hsp90, drug resistance 122–123 azoles, 372 Interferon regulatory factor 8 (IRF8), mutations and echinocandins, 376 fungal infection susceptibility, 151–152 HWP1, 165, 169, 202 Interferon-g (IFN-g), signaling defects and fungal Hydroxyferricrocin, 246 infection susceptibility, 147 Hyphae. See also Morphogenesis Interleukin-2 (IL-2), 148 Aspergillus,13 Interleukin-12 (IL-12), signaling defects and fungal biofilms, 166 infection susceptibility, 147 Cryptococcus neoformans reproduction in formation, Interleukin-17 (IL-17) 42–43 innate immunity, 128–129 dimorphism. See Thermally dimorphic fungi signaling defects and fungal infection susceptibility, infection role, 2–3 147–148 melanization. See Black fungi Intracranial pressure (ICP), elevation management, 343 Hyr1, 164, 202 Invasive aspergillosis (IA) antifungal clinical trials overview, 354–355 I prospects, 355 IA. See Invasive aspergillosis clinical presentation, 439–440 ICL1, 241–243 diagnosis, 440–441 ICP. See Intracranial pressure drug development Ifd6, 371 overview, 354–355 IFN-g. See Interferon-g prospects, 355 IL-2. See Interleukin-2 drug resistance. See Drug resistance IL-12. See Interleukin-12 ecology, 433 IL-17. See Interleukin-17 epidemiology, 440 ILC. See Innate lymphoid cell history of study, 431–432 Immune reconstitution syndrome (IRS), 330, 344 laboratory identification and biology, 433–436 Immunodiffusion, diagnostics, 259 pathogenesis, 436–439 Immunotherapy taxonomy and nomenclature of pathogens, 432–433 antibody therapy, 286–289 treatment, 441–442 dendritic cell immunotherapy, 289–290 IRF8. See Interferon regulatory factor 8 Infection susceptibility Iron anhidrotic ectodermal dysplasia with assimilation, 245–246 immunodeficiency, 153 homeostasis regulation, 246–247 APECED, 150–151 IRS. See Immune reconstitution syndrome chronic granulomatous disease, 141, 146 Itraconazole cytokine signaling disorders adverse effects, 328 interferon-g, 147 black fungus management, 530–531 interleukin-2, 148 candidiasis management, 338 interleukin-12, 147 endemic fungi infection management, 356–357 interleukin-17, 147–148 entomophthoramycosis management, 506

571

K psoriasis, 477 Ketoconazole, endemic fungi infection management, seborrheic dermatitis, 475, 477 356–357 Malassezia globosa,32 KI. See Potassium iodide Malassezia sympodialis,32 Knufia, 526 Manganese, transport, 247 Knufia epidermidis, 526 Mannose receptor (MR), pathogen recognition, KRE6, 280 101–102, 127–128 MAT,75 MAT1-1, 51–52, 75 L MAT1-2, 51–52, 75 Lacazia,7 MATa, 388, 391 Lacazia loboi,4 MCL, pathogen recognition, pathogen recognition, 101 Las17, 199 MCM7, 435 LDF1, 188 MDH1, 242 Legionella pneumophilia, 185 MDR, expression in azole resistance Leptosphaeria, 525 cis-acting elements, 368 LFD6, 172 overview, 368 Lichtheimia trans-acting elements, 368–370 genome studies, 493–494 Medicopsis, 526 mucormycosis. See Mucormycosis Melanin LOH. See Loss of heterozygosity Cryptococcus capsule melanization, 397 Loss of heterozygosity (LOH) pathogens. See Black fungi aneuploidy, 84–86 Mendelian susceptibility to mycobacterial disease drug resistance role, 370 (MSMD), 147 Lung transplantation, lung mycobiome, 558 MEP1, 238 LYP1, 188 MEP2, 238–239 Meristospore, 498 Metabolism. See Carbon assimilation; Iron; Nitrogen M assimilation; Zinc MAC1, 399 Mfa1, 48 Macrophage Mfa1, 48 functional overview, 121–122, 179–180 MFS transporters, 368 pathogen survival and replication MIC. See Minimum inhibitory concentration Aspergillus fumigatus, 184–185 Micafungin, 340, 374 Candida, 180–184 Microsporum,8,31 Coccidiodes, 186–187 Mid1, 206 Cryptococcus, 185–186 Mig1, 241 Histoplasma capsulatum, 187–188 Mincle, pathogen recognition, 101, 127 Madurella, 526 Minimum inhibitory concentration (MIC) Madurella grisea, 526 echinocandins, 311–312 Madurella mycetomatis, 526 efficacy predictions, 304–306 Malassezia flucytosine, 309 evolution, 25 overview, 300–303 genome features, 469 polyenes, 307–308 innate immunity, 101, 127 triazoles, 309–310 morphogenesis, 201 MK-3118, 279 mycobiome analysis of skin, 469–470 Mkc1, 172, 376 overview, 474–475 MLS1, 242 phylogenetic relationships, 468 Mls1, 243 skin diseases Mod5, 198 atopic dermatitis, 475–476 Molecular phylogenetics, fungus evolution, 24–26 dandruff, 475 Monocyte folliculitis, 477 functional overview, 121–122 overview, 467–469 pathogen interactions, 97–98 pathogenesis, 477–478 Monophosphoryl lipid A (MPL), vaccine adjuvant, pityriasis versicolor, 476–477 293–294

572

Morphogenesis prospects, 560 community development, 207–209 skin, 469–470, 554 cytoskeleton, 198 Mycosphaerella graminicola, 33, 201 dimorphism. See Thermally dimorphic fungi MyD88, 125 evolution, 197 Myeloperoxidase (MPO), deficiency and fungal fungal life cycle, 206–207 infection susceptibility, 146–147 hyphae contact sensing, 206 nutritional and environmental signal sensing, N 202–206 NADPH oxidase, defects and fungal infection overview, 195–196 susceptibility, 141, 146 quorum sensing, 206 Natural killer (NK) cell transcriptional regulation, 206 functional overview, 122 niche adaptation and fungal virulence, 200–202 invariant cells, 122–123 polarization, 193–195 Nectria,14 positional markers, 198–199 NEMO, 154 prospects for study, 209 Neosartorya fumigata,51 signal transduction, 199–200 Neosartorya udagawae, 52, 146 vesicle trafficking, 197–198 Neoscytalidium, 526–527 yeast Neoscytalidium dimidiatum, 526 Ascomycetes, 196 Neotestudina,24 Basidiomycetes, 196–197 NET. See Neutrophil extracellular trap Mpk1, 400, 402 Neurospora, 29, 31 MPL. See Monophosphoryl lipid A Neurospora crassa, 26, 28, 34 MPO. See Myeloperoxidase Neutrophil, functional overview, 121 MR. See Mannose receptor Neutrophil extracellular trap (NET), 121, 438 MRR1, 86, 369 NGT1, 205 MSMD. See Mendelian susceptibility to mycobacterial NGT2, 205 disease Nitrogen assimilation MST1, mutation and fungal infection susceptibility, 154 host niches, 237–239 MTL, 47, 49, 167, 419 overview, 236–237 Mucorales, 14–15, 25, 227–229, 484–485, 490 peptide and amino acid transporters, 237 Mucor circillenoides, 15, 493–494 proteases, 237 Mucormycosis regulation, 239–240 genome studies NK cell. See Natural killer cell Lichtheimia, 493–494 NLRC4, 130 miscellaneous genomes, 494 NLRP3, 130 Mucor circillenoides, 493 Nod-like receptors, 129–130 Rhizopus, 490–493 NRG1, 203–204, 206 host–pathogen interactions, 486–487 nsdD, 52 pathogens, 484–485 NSF, 198 susceptibility factors, 485–486 treatment O combination therapy, 488–489 Ochoconis, 527 iron chelation therapy, 489–490 Ofd1, 204 monotherapy, 487–488 Onygenales, 4–8, 24 overview, 487 Ophiocordyceps,24 Mycobacterium tuberculosis, 5, 101 Ophiostoma,53 Mycobiome Ophiostoma ulmi, 201 Candida vaginosis, 560 Oropharyngeal candidiasis, 129 Clostridium difficile diarrhea, 558–560 OXR1, 188 development in humans, 555–556 inflammatory bowel disease, 558–560 lung mycobiome and lung transplantation, 558 P mapping, 554–555 Paecilomyces lilacinus, 146 oral mycobiome and HIV, 556–558 Paecilomyces variotii, 146

573

PAFE. See Postantifungal effect amphotericin B lipid formulations, 307–308 Paracoccidiodes, 7, 10, 31 clinical implications, 308 Paracoccidiodes brasiliensis concentration effect, pharmacodynamic index, amino acid metabolism, 240 and target, 307 dendritic cell immunotherapy, 290 triazoles innate immunity, 121 clinical implications, 310–311 morphogenesis, 201 concentration effect, pharmacodynamic index, overview, 4 and target, 309–310 T-cell immunity, 102 Pharmacokinetics, antifungals thermal dimorphism, 456–457 animal models, 301 Paracoccidiodes lutzii,4 combination therapy analysis, 312–313 Parnafungin A, 279 epithelial lining fluid measurements, 299–300 Pattern recognition receptors. See specific receptors experimental measures and predictions, 301–307 Pbs2, 204 in vitro studies, 300–301 PBX1,67 overview, 299–300 PBX2,67 Phialophora, 527 Pck1, 241 Phialophora europaea, 527 Pcl103, 197 Phoma, 527–528 PcMei2, 548 Phospholamban (PLB), 186 PCP. See Pneumocystis pneumonia Phospholipase B, 398 PCR. See Polymerase chain reaction Phospholipase D (PLD), 225 PcRan1, 548 Phosphoraceae, 519 PDR transporters, 367, 369–370 Phosphoraceae europaea, 520 PDR1, 420 Phr1, 172 Penicillium, 24, 30 Pityriasis versicolor (PV), Malassezia role, 476–477 Penicillium marneffii PKA. See Protein kinase A evolution, 27 PKC. See Protein kinase C morphogenesis, 201 PLB. See Phospholamban overview, 5 PLB1, 398 thermal dimorphism, 458–460 PLD. See Phospholipase D Pes1, 207 Ploidy change. See also Aneuploidy PFK2, 242–243 overview, 73–75 Phaeoacremonium, 527 sexual reproduction mediation Phaeoacremonium alvesii, 527 endoreduplication and mitotic collapse, 79–80 Phaeoacremonium amstelodamense, 527 meiosis versus parasex, 78–79 Phaeoacremonium griseorubrum, 527 overview, 75–76 Phaeoacremonium inflatipes, 527 parasexual reproduction mediation, 76–78 Phaeoacremonium krajdenii, 527 Pneumocystis Phaeoacremonium parasiticum, 527 epidemiology, 540 Phaeoacremonium rubrigenum, 527 evolution, 24 Phaeoacremonium tardicrescens, 527 history of study, 539 Phaeoacremonium venezuelense, 527 innate immunity, 104 Pharmacodynamics, antifungals life cycle, 540–541 animal models, 301 morphology, 541–542 combination therapy analysis, 312–313 systematic position within Fungi, 540 echinocandins unique features, 546–547 clinical implications, 312 virulence factors and drug targets, 547–548 concentration effect, pharmacodynamic index, Pneumocystis carinii and target, 311–312 biofilm, 162 experimental measures and predictions, 301–307 innate immunity, 126–127 flucytosine life cycle, 541 clinical implications, 309 morphology, 542 concentration effect, pharmacodynamic index, Pneumocystis jirovecii and target, 308–309 cell invasion, 228–229 in vitro studies, 300–301 morphology, 542 polyenes overview, 7, 14, 540–542

574

Pneumocystis murina Q biofilm, 162 Quorum sensing, hyphal morphogenesis, 206 innate immunity, 122 life cycle, 541 morphology, 542 R Pneumocystis pneumonia (PCP) RAC1, 199–200 animal models, 544–545 RAC2, 199–200 diagnosis, 543 Ramichloridium,14 epidemiology, 540 Ras1, 199, 203, 206–208 pathogenesis, 543–546 Ras2, 203 treatment, 543 Rax1, 198 Polarity. See Morphogenesis Rax2, 198 Polymerase chain reaction (PCR), diagnostics, Reproduction, sexual 259–262, 264 Aspergillus fumigatus Population genetics drug resistance role, 53 Cryptococcus neoformans reproduction studies, other Aspergillus species, 521 45–47 overview, 51 fungus evolution, 26–30 pathogen population biology significance, 52–53 Population genomics, fungus evolution, 32–35 sexual cycle, 51–52 Posaconazole Candida albicans parasexual reproduction, 47–51 candidiasis management, 338 Cryptococcus neoformans a-a opposite sex bisexual indications, 274 reproduction pharmacokinetics and pharmacodynamics, genetic hybrid studies, 44 327–328 monokaryotic fruiting, 43 structure, 273 overview, 42 Postantifungal effect (PAFE), 302, 307, 309 population genetics studies, 45–47 Potassium iodide (KI), entomophthoramycosis unisexual reproduction, 43–44 management, 506–507 virulence links, 47 PRA1, 247 overview, 41–42 PRB1, 239 ploidy change mediation PRB2, 239 endoreduplication and mitotic collapse, 79–80 PRC1, 239 meiosis versus parasex, 78–79 Protein kinase A (PKA) overview, 75–76 high osmolarity glycerol response, parasexual reproduction mediation, 76–78 400–401 prospects for study, 53–54 morphogenesis role, 203–205 Respiratory tract, innate immunity, 124 Protein kinase C (PKC) RHAMM, 227 biofilm formation role, 172–173 Rhinocladiella, 528 high osmolarity glycerol response, 400–401 Rhinocladiella aquaspersa, 528 Proteomics, diagnostics, 262–263 Rhinocladiella basitona, 528 Pseudalescheria,24 Rhinocladiella similis, 528 Pseudoallescheria boydii,14 Rhinosporidium,25 Pseudochaetosphaeronema, 528 Rhizopus, 15, 25. See also Mucormycosis Pseudochaetosphaeronema larense, 528 Rhizopus delemar, 492–493 Pseudomonas aeruginosa, biofilm, 166, 168 Rhizopus microsporus, 491, 493 Psoriasis, Malassezia role, 477 Rhizopus oryzae, 15, 485–486, 488, 492–493 Ptp2, 204 Rhizopus stolonifer, 491 Ptp3, 204 Rho1, 195, 199 PV. See Pityriasis versicolor Rho101, 197 PYK1, 242–243 Rho104, 197 Pyrenochaeta, 528 Ribosomal DNA Pyrenochaeta keratinophila, 528 diagnostics, 261 Pyrenochaeta mackinnonii, 528 molecular phylogenetics, 24 Pyrenochaeta romeroi, 528 Rim20, 205 Pyrenochaeta unguis-hominis, 528 Rim21, 205 Pythium insidiosum,25 Rim101, 197, 247

575

RLM1, 172 Sod4, 183 Rlm1, 374 SOK1, 206 RodA, 224 SOU1,83 RPB1, 435 SOWgp, 187, 454 RPB2, 435 SPA, 438 RPM1, 170 Spa2, 207 Rtt109, 548 SPD, 438 Sporothrix,24 Sporothrix schenckii S overview, 5 Saccharomyces cerevisiae,10 cell invasion, 229 carbon assimilation, 241–242 thermal dimorphism, 457–458 cross-species genetic interaction mapping, 67 SrcA, 246 dendritic cell response, 96 SRE1, 400 evolution, 26–29, 33 SreA, 247 genome profiling SREBP, pathway in Cryptococcus neoformans virulence, functional annotation, 63–64 66–67 libraries, 62–63 Ssa1, 221–222 systematic approach, 63 Ssk2, 204 morphogenesis, 197–199, 452 Ssy5, 239 ploidy change, 73–75, 79, 82–82 Staphylococcus aureus, 168, 260 reproduction, 47 STAT1, mutations and fungal infection susceptibility, Saccharomyces paradoxus,33 149–150 Sap2, 237, 293 STAT3, 129, 148–149 Scedosporium anamorphs,14 STK4, mutation and fungal infection susceptibility, 154 SCH B, 278–279 Stp1, 239 Schizophyllum commune,26 Stp2, 238–239 Schizosaccharomyces pombe Surfactant protein D, 229 morphogenesis, 197–198 Susceptibility. See Infection susceptibility ploidy change, 73–75 SCID. See Severe combined immunodeficiency Scp1, 400 T SD. See Seborrheic dermatitis TAC 1 , 77, 85–86, 368, 370–371 Seborrheic dermatitis (SD), Malassezia role, 475, 477 TAFC, 246 SEC6, 399 Talaromyces marneffii. See Penicillium marneffii Sef1, 246 Tapesia yallundae,53 SET3, 419 T cell Severe combined immunodeficiency (SCID), 148 CD8 T cells, 107 Sexual reproduction. See Reproduction, sexual regulatory T cells, 106–107 SFL1, 183 Th1 immunity, 102–103 SFL2, 419 Th2 immunity, 103–104 Sfu1, 246 Th17 immunity, 104–106 SID1, 188 Tea1, 198 SID3, 188 Terbinafine, black fungus management, 530 SID4, 188 TGF-b. See Transforming growth factor-b Sit1, 246, 399 Thermally dimorphic fungi Skin overview, 449–450, 452 diseases. See specific diseases and pathogens origins, 449–451 innate immunity, 123–124 phylogenetic analysis of pathogens, 451 Slt2, 376 Blastomyces dermatitides, 452–453 SMI1, 172 Coccidiodes immitis, 453–454 Smi1, 374 Coccidiodes posadasii, 453–454 Snf5, 69 Histoplasma capsulatum, 454–456 SNQ2, 367 Paracoccidiodes brasiliensis, 456–457 SOD1, 186 Sporothrix schenckii, 457–458 Sod1, 183 Penicillium marneffii, 458–460

576

TLR. See Toll-like receptor V TNF-a. See Tumor necrosis factor-a Vaccination Toll-like receptor (TLR), overview, 98–99, 125–126 attenuated vaccines, 291–292 TPK1, 168 conjugate vaccines, 293–294 Tpk1, 203 dendritic cell vaccination, 290 Tpk2, 203 killed vaccines, 291–292 Transforming growth factor-b (TGF-b), cell invasion overview, 291 enhancement, 228–229 recombinant protein vaccines, 292–293 Treatment principles, mold infection Valley fever, 186 acute versus chronic treatment, 330 Veronaea, 529 adverse effects of antifungal drugs, 328–329 Veronaea botrysa, 529 Candida. See Candida treatment principles Verruconis, 529 Cryptococcus. See Cryptococcus treatment principles Verticillium, 201 early diagnosis, 329 Virulence factors, criteria for pathogenicity, 2–3 epidemiology in local area, 329 Vomocytosis, 186 evidence-based treatment guidelines, 331–332 Voriconazole immunosuppression level of patient, 330 adverse effects, 328–329 multidisciplinary approach, 330–331 black fungus management, 531 overview, 323–324 candidiasis management, 338–340 pathogenesis and natural history of infection, 325–326 invasive aspergillosis management, 355–356, 442 pharmacokinetics and pharmacodynamics, 326–328 mechanism of action, 273–274 spectrum of activity of antifungal drugs, 324 mucormycosis management, 488 Trematosphaeria, 528–529 pharmacokinetics and pharmacodynamics, 327 Trematosphaeria grisea, 528 structure, 273 Trichophyton, 8, 24, 31, 124 Vulvovaginal candidiasis (VVC), 125, 560 Trichophyton rubrum, 29, 202 VVC. See Vulvovaginal candidiasis Trichosporon,25 Trimethoprim-sulfamethoxazole, Pneumocystis pneumonia management, 543 X TSR1, 435 Xog1, 172 Tumor necrosis factor-a (TNF-a), fungus immune response, 102 Tup1, 244, 247 Y TYK2, deﬁciency and fungal infection susceptibility, 153 YAP1, 183 Yap1, 207, 438 YHB1, 183 U Yps3, 6, 202, 455 ubi4, 239 Ubr1, 206 Umbelopsis ramannniana, 494 Z UME6, 419–420 ZAP1, 399 Ume6, 204, 207 Zap1, 172, 371 Uncinocarpus reesii,31 ZCF39, 419 UPC2,85 Zinc, assimilation, 247–248 URA3,68 Znf2, 209 URE1, 186, 398–399 ZO-1, 226 Ure1, 226 ZrfC, 247 Urease, 238, 398–399, 454 Zrt1, 247 Ustilago maydis, 201, 207 Zygospore, 498

577