Azole resistance in Candida spp. isolated from Catú Lake, Ceará, Brazil: an efflux-pump-mediated mechanism

Abstract

Since, there is no study reporting the mechanism of azole resistance among yeasts isolated from aquatic environments; the present study aims to investigate the occurrence of antifungal resistance among yeasts isolated from an aquatic environment, and assess the efflux-pump activity of the azole-resistant strains to better understand the mechanism of resistance for this group of drugs. For this purpose, monthly water and sediment samples were collected from Catú Lake, Ceará, Brazil, from March 2011 to February 2012. The obtained yeasts were identified based on morphological and biochemical characteristics. Of the 46 isolates, 37 were Candida spp., 4 were Trichosporon asahii, 3 were Cryptococcus laurentii, 1 Rhodotorula mucilaginosa, and 1 was Kodamaea ohmeri. These isolates were subjected to broth microdilution assay with amphotericin B, itraconazole, and fluconazole, according to the methodology standardized by the Clinical and Laboratory Standards Institute (CLSI). The minimum inhibitory concentrations (MICs) of amphotericin B, itraconazole, and fluconazole were 0.03125–2 μg/mL, 0.0625 to ≥16 μg/mL, and 0.5 to ≥64 μg/mL, respectively, and 13 resistant azole-resistant Candida isolates were detected. A reduction in the azole MICs leading to the phenotypical reversal of the azole resistance was observed upon addition of efflux-pump inhibitors. These findings suggest that the azole resistance among environmental Candida spp. is most likely associated with the overexpression of efflux-pumps.

Differences in epidemiology of candidaemia in the Nordic countries – what is to blame?

“…It has also been reported that azole‐resistant Candida isolates have been found in lake water and in a porcupine in Brazil. The resistance were mediated by efflux pumps . Whether these findings have implications for human infection is unknown as our study was not designed to reveal associations between agricultural azoles and candidaemia or Candida resistance.…”

“…The resistance were mediated by efflux pumps. 30,31 Whether these findings have implications for human infection is unknown as our study was not designed to reveal associations between agricultural azoles and candidaemia or Candida resistance. Another study design is needed to discover any association.…”

“…Susceptibility was categorised according to EUCAST breakpoint tables for interpretation of MICs version 8.0. 17 We defined an episode of candidaemia as at least one blood-culture positive for Candida species and episodes were considered unique if they occurred at least 30 Antibacterial and antifungal sales numbers from the hospital care sector (HCS) and primary care sector (PCS) were available from the ECDC database and from drug consumption statistics from each country (www.ecdc.europe.ec, www.fimea.fi, www.medstat.dk, www.socialstyrelsen.se, www.fhi.no).…”

Antifungal susceptibility of yeasts isolated from anthropogenic watershed

“…In their work, the authors observed that yeast derived from freshwater lakes with resistance to fluconazole and itraconazole had the activity of its efflux pumps inhibited by the addition of promethazine and haloperidol. MIC tests performed after this test resulted in a reversal of the azole-resistant An Acad Bras Cienc 2019) 91(1e20170369 9 | 12 phenotype, indicating a direct involvement of the efflux pumps in the drug sensitivity of yeast (Brilhante et al 2016). The sequencing of isolates was performed in this study to identify samples with resistance to amphotericin B, resulting in seven isolates belonging to the genus Candida.…”

“…The hypothesis that antifungal resistance of yeasts could be achieved through exposure to nonspecific compounds derived from various sources of pollution has been reinforced in a recent study published by Brilhante et al (2016). In their work, the authors observed that yeast derived from freshwater lakes with resistance to fluconazole and itraconazole had the activity of its efflux pumps inhibited by the addition of promethazine and haloperidol.…”