Abstract
Cryptococcosis is a common opportunistic infection in patients with advanced HIV infection and may also affect immunocompetent patients. The available antifungal agents are few and other options are needed for the cryptococcosis treatment. In this work, we first analyzed the virulence of twelve C. neoformans and C. gattii strains assessing capsule thickness, biofilms formation, and survival and morbidity in the invertebrate model of Galleria mellonella and then we evaluated the antifungal activity of voriconazole (VRC) in vitro and in vivo also using G. mellonella. Our results showed that all Cryptococcus spp. isolates were able to produce capsule and biofilms, and were virulent using G. mellonella model. The VRC has inhibitory activity on planktonic cells with MIC values ranging from 0.03 to 0.25 μg/mL on Cryptococcus spp.; and these isolates were more tolerant to fluconazole (ranging from 0.25 to 16 μg/mL), the triazol agent often recommended alone or in combination with amphotericin B in the cryptococcosis therapy. In contrast, mature biofilms were less susceptible to the VRC treatment. The VRC (10 or 20 mg/kg) treatment of infected G. mellonella larvae significantly increased the larval survival when compared to the untreated group for the both Cryptococcus species and significantly decreased the fungal burden and dissemination in the larval tissue. Our findings corroborate with the literature data, supporting the potential use of VRC as an alternative for cryptococcosis treatment. Here, we emphasize the use of G. mellonella larval model as an alternative animal model for studies of antifungal efficacy on mycosis, including cryptococcosis.
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Funding
This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP—Brasil, Grants 2015/07993-0 and 2017/19374-9) and in part by the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq—Brasil) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Brasil, Finance Code 001). Cristina de Castro Spadari and Fernanda Walt Mendes da Silva de Bastiani were participants of the fellowship program from CAPES.
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FWMSB and PBBP designed and performed all experiments and analyzed data. ASAM contributed with the Cryptococcus clinical isolates. CCS and KI analyzed all data and wrote the manuscript. All authors revised the article, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.
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Communicated by Erko Stackebrandt.
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de Castro Spadari, C., da Silva de Bastiani, F.W.M., Pisani, P.B.B. et al. Efficacy of voriconazole in vitro and in invertebrate model of cryptococcosis. Arch Microbiol 202, 773–784 (2020). https://doi.org/10.1007/s00203-019-01789-8
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DOI: https://doi.org/10.1007/s00203-019-01789-8