The development of animal infection models and antifungal efficacy assays against clinical isolates of Trichosporon asahii, T. asteroides and T. inkin. 2015

Marçal Mariné, and Vinicius Leite Pedro Bom, and Patricia Alves de Castro, and Lizziane Kretli Winkelstroter, and Leandra Naira Ramalho, and Neil Andrew Brown, and Gustavo Henrique Goldman
a Faculdade de Ciências Farmacêuticas de Ribeirão Preto; Universidade de São Paulo ; São Paulo , Brazil.

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.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007814 Larva Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. Maggots,Tadpoles,Larvae,Maggot,Tadpole
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009036 Moths Insects of the suborder Heterocera of the order LEPIDOPTERA. Antheraea,Giant Silkmoths,Giant Silkworms,Silkmoths, Giant,Silkworms, Giant,Antheraeas,Giant Silkmoth,Giant Silkworm,Moth,Silkmoth, Giant,Silkworm, Giant
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000077336 Caspofungin A cyclic lipopeptide echinocandin and beta-(1,3)-D-glucan synthase inhibitor that is used to treat internal or systemic MYCOSES. Cancidas,Caspofungin Acetate,Caspofungin MSD,L 743,872,L 743872,L-743,872,L-743872,MK 0991,MK-0991,L743,872,L743872,MK0991
D000666 Amphotericin B Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. Amphocil,Amphotericin,Amphotericin B Cholesterol Dispersion,Amphotericin B Colloidal Dispersion,Fungizone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D014250 Trichosporon A mitosporic fungal genus causing opportunistic infections, endocarditis, fungemia, a hypersensitivity pneumonitis (see TRICHOSPORONOSIS) and white PIEDRA. Trichosporons

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