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Published on: December 28, 2017
Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and
Suélen A Rossi1, Nuria Trevijano-Contador2, Liliana Scorzoni1
1Faculdade de Ciências Farmacêuticas, UNESP - Universidade Estadual Paulista, Campus Araraquara, Departamento de Análises Clíncas São Paulo, Brazil.
Abstract:
Cryptococcus sp. are responsible for around 1 million cases of meningitis every year. Fluconazole (FLU) is commonly used in the treatment of cryptococcosis, mainly in immunocompromised patients and the resistance is usually reported after long periods of treatment. In this study, the morphological characterization and virulence profile of FLU-susceptible and FLU-resistant clinical and environmental isolates of C. neoformans and C. gattii were performed both in vitro and in vivo using the Galleria mellonella model. FLU-susceptible isolates from C. neoformans were significantly more virulent than the FLU-resistant isolates. FLU-susceptible C. gattii isolates showed a different virulence profile from C. neoformans isolates where only the environmental isolate, CL, was more virulent compared with the resistant isolates. Cell morphology and capsule size were analyzed and the FLU-resistant isolates did not change significantly compared with the most sensitive isolates. Growth at 37°C was also evaluated and in both species, the resistant isolates showed a reduced growth at this temperature, indicating that FLU resistance can affect their growth. Based on the results obtained is possible suggest that FLU resistance can influence the morphology of the isolates and consequently changed the virulence profiles. The most evident results were observed for C. neoformans showing that the adaptation of isolates to antifungal selective pressure influenced the loss of virulence.
Insights
Antifungal resistance in Cryptococcus species can reduce their virulence, particularly in Cryptococcus neoformans. Fluconazole resistance may impact fungal growth and morphology, leading to decreased pathogenicity.
Area of Science:
- Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Cryptococcus species cause approximately 1 million meningitis cases annually.
- Fluconazole (FLU) is a primary treatment for cryptococcosis, especially in immunocompromised individuals.
- Antifungal resistance often emerges after prolonged treatment periods.
Purpose of the Study:
- To investigate the morphological characteristics and virulence of fluconazole-susceptible and fluconazole-resistant Cryptococcus neoformans and Cryptococcus gattii isolates.
- To compare virulence profiles in vitro and in vivo using the Galleria mellonella model.
- To assess the impact of fluconazole resistance on fungal morphology, capsule size, and growth at 37°C.
Main Methods:
- Morphological characterization of clinical and environmental isolates.
- Virulence profiling using the Galleria mellonella infection model.
- In vitro analysis of cell morphology, capsule size, and growth at 37°C.
Main Results:
- Fluconazole-susceptible Cryptococcus neoformans isolates exhibited significantly higher virulence than resistant isolates.
- Fluconazole-susceptible Cryptococcus gattii isolates displayed varied virulence; only one environmental isolate was more virulent than resistant ones.
- Fluconazole-resistant isolates showed reduced growth at 37°C compared to susceptible isolates.
- No significant changes in cell morphology or capsule size were observed between susceptible and resistant isolates.
Conclusions:
- Fluconazole resistance can influence fungal morphology and alter virulence profiles.
- Adaptation to antifungal selective pressure, particularly in Cryptococcus neoformans, can lead to a loss of virulence.
- Fluconazole resistance may compromise the growth of Cryptococcus species at host physiological temperatures.
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