antifungal susceptibility profile and potential virulence-associated [PDF]

OLIVEIRA, R.M.1. INSTITUTION: 1Laboratório de Micologia, Instituto Nacional de Infectologia Evandro. Chagas, Fundação

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TITLE: ANTIFUNGAL SUSCEPTIBILITY PROFILE AND POTENTIAL VIRULENCE-ASSOCIATED ATTRIBUTES IN BRAZILIAN CLINICAL STRAINS OF CANDIDA GLABRATA AND CANDIDA NIVARIENSIS AUTHORS: FIGUEIREDO-CARVALHO, M.H.G.1; RAMOS, L.S.2; BARBEDO, L.S.1; OLIVEIRA, J.C.A.1; SANTOS, A.L.S.2; ALMEIDA-PAES, R.1; ZANCOPÉOLIVEIRA, R.M.1 INSTITUTION: 1Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 2Laboratório de Investigação de Peptidases, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. ABSTRACT: Candida glabrata, Candida nivariensis, and Candida bracarensis are opportunistic human fungal pathogens that comprise the Candida glabrata species complex. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to eight antifungal agents, the production of seven hydrolytic enzymes related to fungal virulence, the biofilm formation, and the relationship between these phenotypes in 91 clinical strains of C. glabrata and in 01 clinical strain of C. nivariensis identified by sequencing of ITS15.8S-ITS2 region of the rDNA. Thirteen haplotypes comprising the C. glabrata strains and one with the C. nivariensis strain were generated after ITS sequencing. All studied strains were susceptible to flucytosine. However, C. glabrata strains showed resistance to amphotericin B (9.9%), fluconazole (15.4%), itraconazole (5.5%), caspofungin (8.8%), or micafungin (15.4%). High minimum inhibitory concentrations (MICs) were found for voriconazole and posaconazole. Fluconazole and micafungin resistance was also noted in C. nivariensis. Overall, C. glabrata clinical strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Candida nivariensis was excellent producer of aspartic protease, good producer of catalase and phytase, but no in vitro activity was detected for the other enzymes tested. Candida glabrata and C. nivariensis were able to produce biofilm. In general, those biofilms presented low biomass, but high metabolic activity. In C. glabrata strains, statistically significant correlations were identified between micafungin MIC and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections. Keywords: antifungal, Candida glabrata, Candida nivariensis, hydrolytic enzymes Development Agency: CNPq

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