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

被引:21
作者
Rossi, Sueen A. [1 ]
Trevijano-Contador, Nuria [2 ]
Scorzoni, Liliana [1 ]
Cecilia Mesa-Arango, Ana [3 ]
de Oliveira, Haroldo C. [1 ]
Werther, Karin [4 ]
Raso, Tania de Freitas [4 ]
Mendes-Giannini, Maria J. S. [1 ]
Zaragoza, Oscar [2 ]
Fusco-Almeida, Ana M. [1 ]
机构
[1] UNESP Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Anal Clin, Campus Araraguara, Sao Paulo, Brazil
[2] Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Micol, Madrid, Spain
[3] Univ Antioquia, Dermatol Res Grp, Medellin, Colombia
[4] Univ Sao Paulo, Dept Patol, Fac Med Vet & Zootecnia, Sao Paulo, Brazil
关键词
Cryptococcus sp; resistance; fluconazole; virulence; Galleria mellonella; EPIDEMIOLOGIC CUTOFF VALUES; TRANSPORTER-ENCODING GENE; END-POINT DISTRIBUTIONS; CANDIDA-ALBICANS; GALLERIA-MELLONELLA; SPECIES COMPLEX; VAR; GRUBII; LANOSTEROL; 14-ALPHA-DEMETHYLASE; PATHOGEN CRYPTOCOCCUS; FUNGAL PATHOGENS;
D O I
10.3389/fmicb.2016.00153
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 degrees 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.
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页数:14
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