AUTHOR=Rossi Suélen A. , Trevijano-Contador Nuria , Scorzoni Liliana , Mesa-Arango Ana Cecilia , de Oliveira Haroldo C. , Werther Karin , de Freitas Raso Tânia , Mendes-Giannini Maria J. S. , Zaragoza Oscar , Fusco-Almeida Ana M. 

TITLE=Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and Cryptococcus gattii Isolates

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00153

DOI=10.3389/fmicb.2016.00153

ISSN=1664-302X

ABSTRACT=<p><italic>Cryptococcus</italic> 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 <italic>C. neoformans</italic> and <italic>C. gattii</italic> were performed both <italic>in vitro</italic> and <italic>in vivo</italic> using the <italic>Galleria mellonella</italic> model. FLU-susceptible isolates from <italic>C. neoformans</italic> were significantly more virulent than the FLU-resistant isolates. FLU-susceptible <italic>C. gattii</italic> isolates showed a different virulence profile from C. <italic>neoformans</italic> 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 <italic>C. neoformans</italic> showing that the adaptation of isolates to antifungal selective pressure influenced the loss of virulence.</p>