The development of animal infection models and antifungal efficacy assays against clinical isolates of Trichosporon asahii, T. asteroides and T. inkin.
The present study developed Galleria mellonella and murine infection models for the study of Trichosporon infections. The utility of the developed animal models was demonstrated through the assessment of virulence and antifungal efficacy for 7 clinical isolates of Trichosporon asahii, T. asteroides and T. inkin. The susceptibility of the Trichosporon isolates to several common antifungal drugs was tested in vitro using the broth microdilution and the E-test methods. The E-test method depicted a lower minimal inhibitory concentration (MIC) for amphotericin and a slightly higher MIC for caspofungin, while MICs observed for the azoles were different but comparable between both methods. All three Trichosporon species established infection in both the G. mellonella and immunosuppressed murine models. Species and strain dependent differences were observed in both the G. mellonella and murine models. T. asahii was demonstrated to be more virulent than the other 2 species in both animal hosts. Significant differences in virulence were observed between strains for T. asteroides in the murine model. In both animal models, fluconazole and voriconazole were able to improve the survival of the animals compared to the untreated control groups infected with any of the 3 Trichosporon species. In G. mellonella, amphotericin was not able to reduce mortality in any of the 3 species. In contrast, amphotericin was able to reduce murine mortality in the T. asahii or T. inkin models, respectively. Hence, the developed animal infection models can be directly applicable to the future deeper investigation of the molecular determinants of Trichosporon virulence and antifungal resistance.
a Faculdade de Ciências Farmacêuticas de Ribeirão Preto; Universidade de São Paulo ; São Paulo , Brazil.
Marçal
M
Mariné
Vinicius Leite Pedro
VL
Bom
Patricia Alves
PA
de Castro
Lizziane Kretli
LK
Winkelstroter
Leandra Naira
LN
Ramalho
Neil Andrew
NA
Brown
Gustavo Henrique
GH
Goldman
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077336:Caspofungin; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology / Q000627:therapeutic use; D015725:Fluconazole / Q000627:therapeutic use; D016867:Immunocompromised Host; D007668:Kidney / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007814:Larva / Q000382:microbiology; D055666:Lipopeptides; D051379:Mice; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000382:microbiology*; D014250:Trichosporon / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity* / Q000648:ultrastructure; D060586:Trichosporonosis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D065819:Voriconazole / Q000494:pharmacology / Q000627:therapeutic use
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000666:Amphotericin B; D015725:Fluconazole; D000077336:Caspofungin; D065819:Voriconazole
AMB, Amphotericin B; CFG, Caspofungin; CLSI, Clinical Laboratory Standards Institute; FLC, Fluconazole; GMS, Gomori methenamine silver; Galleria mellonella; ITZ, Itraconazole; MIC, Minimal Inhibitory Concentration; PBS, Phosphate Buffered Saline; PSC, Posaconazole; SDA, Sabouraud Dextrose Agar; Trichosporon; VRC, Voriconazole; antifungal; experimental infection; murine model