Detection of ERG11 Overexpression in Candida albicans isolates from environmental sources and clinical isolates treated with inhibitory and subinhibitory concentrations of fluconazole

• Published in: Mycoses Vol. 64; no. 2; pp. 220 - 227
• Main Authors: Morais Vasconcelos Oliveira, Josimary, Conceição Oliver, Josidel, Latércia Tranches Dias, Amanda, Barbosa Padovan, Ana Carolina, Siqueira Caixeta, Ester, Caixeta Franco Ariosa, Marília
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-02-2021
• Subjects: American Type Culture Collection; antifungal; Candida albicans; Clinical isolates; ERG11; ERG11 gene; Fluconazole; gene expression; Minimum inhibitory concentration; Molecular modelling; subinhibitory concentrations; Candida albicans; ERG11; antifungal; fluconazole; subinhibitory concentrations; gene expression
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/myc.13208

Background
Candida species can cause serious infection in patients with changes in defence mechanisms and/or when anatomical barriers are compromised. Mutations and overexpression in the ERG11 gene are described as molecular mechanisms of azole resistance. Information is limited on these mechanisms in the presence of subinhibitory concentrations of fluconazole.
Objectives
This study aimed to evaluate the expression of ERG11 gene from Candida albicans isolates, from clinical and hospital environments, in the absence and presence of inhibitory and subinhibitory concentrations of fluconazole.
Methods
The American Type Culture Collection 10231 strain, five clinical isolates and three isolates from hospital environment colonisation were exposed to inhibitory and subinhibitory concentrations of fluconazole. Susceptibility tests were performed according to EUCAST 7.1 guidelines, and the relative expression analysis of ERG11 was performed by qPCR.
Results
Differences in response to fluconazole concentrations were observed, with the exception only one clinical isolate when treated with 1/4 of the FLU‐minimum inhibitory concentration (MIC). All the other isolates, regardless of the isolation source, had an increase in expression. The overexpression occurred in a very broad range, from 1.086 to 126.105 times. In general, treatment with the highest dose of fluconazole (MIC) was the one that most influenced the ERG11 expression, followed by treatments with 1/2 and 1/4 MIC.
Conclusions
The increased expression of ERG11 by C albicans in the presence of different concentrations of fluconazole is relevant, raising concerns in the care and cleaning of the hospital environment and the prophylactic use of fluconazole that could lead to the selection of potential azole‐resistant isolates.