The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

Abstract

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 Etest 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.

Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model

“…Furthermore, the survival curve profiles for both species were similar in this model, as previously described [13]. In most other studies, antifungal drugs were administered within the first 4 h post-infection [16,18,22,28] and we choose to administer AmB and itraconazole at 1 h post-infection. Following administration of AmB at 0.5, 1 or 2 mg/kg, a dose-dependent survival curve was produced.…”

“…[15], Candida [16,17] and Trichosporon spp. [18] have been successfully performed in a Galleria mellonella infection model. It has important advantages as a fungal host study model: larvae can be incubated at temperatures between 25°C and 37°C, enabling the habitat and conditions of infection in mammals to be simulated; exact amounts of pathogens can be administered; and the viability of the larvae can easily be detected by the lack of movement and melanisation response after infection [19].…”

Evaluating and Improving Vitek MS for Identification of Clinically Relevant Species of Trichosporon and the Closely Related Genera Cutaneotrichosporon and Apiotrichum

“…These genera are intrinsically resistant to echinocandins, and resistance to other antifungal classes has been described (2,4). Moreover, a distinct interspecies antifungal susceptibility profile, virulence, and pathogenicity have been suggested (2,6). Thus, correct identification of these opportunistic pathogens not only at the genus level, but also at the species level, is recommended for optimal clinical management and/or for epidemiological purposes.…”

Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review

“…[32,33,[45][46][47][48][49][50][51], Aspergillus spp. [13,29,35,[52][53][54][55][56][57][58][59][60][61], Mucorales [62][63][64], Madurella mycetomatis [65][66][67], and other fungal agents [68][69][70]. The contribution of G. mellonella to the evaluation of antifungal drugs will be detailed in the following paragraphs.…”

“…In a recent study, G. mellonella was evaluated as an animal model of Trichosporon spp. infection [68]. The authors compared the susceptibility of Trichosporon strains to three antifungals drugs in vitro and in vivo in two animal models (mice and G. mellonella).…”