Frequency of azole resistance in clinical and environmental strains of Aspergillus fumigatus in Turkey: a multicentre study

Abstract

Objectives Aspergillus fumigatus causes several diseases in humans and azole resistance in A. fumigatus strains is an important issue. The aim of this multicentre epidemiological study was to investigate the prevalence of azole resistance in clinical and environmental A. fumigatus isolates in Turkey. Methods Twenty-one centres participated in this study from 1 May 2018 to 1 October 2019. One participant from each centre was asked to collect environmental and clinical A. fumigatus isolates. Azole resistance was screened for using EUCAST agar screening methodology (EUCAST E.DEF 10.1) and was confirmed by the EUCAST E.DEF 9.3 reference microdilution method. Isolates with a phenotypic resistance pattern were sequenced for the cyp51A gene and microsatellite genotyping was used to determine the genetic relationships between the resistant strains. Results In total, resistance was found in 1.3% of the strains that were isolated from environmental samples and 3.3% of the strains that were isolated from clinical samples. Mutations in the cyp51A gene were detected in 9 (47.4%) of the 19 azole-resistant isolates, all of which were found to be TR34/L98H mutations. Microsatellite genotyping clearly differentiated the strains with the TR34/L98H mutation in the cyp51A gene from the strains with no mutation in this gene. Conclusions The rate of observed azole resistance of A. fumigatus isolates was low in this study, but the fact that more than half of the examined strains had the wild-type cyp51A gene supports the idea that other mechanisms of resistance are gradually increasing.

Five‐year surveillance study of clinical and environmental Triazole‐ResistantAspergillus fumigatus isolates in Iran

“…Studies showed that triazole‐resistant Aspergillus strains compared to susceptible ones have elevated mortality rates (>20%), despite the application of appropriate antifungal therapy 2,50,51 . Recently, Cao et al, showed that the prevalence rates of A. fumigatus were 45.8%, 64.7% and 62.5% in environmental samples collected in 2014, 2016 and 2018, respectively, which is consistent with their previous reports showing a range of 35% to 77.8% 52–54 .…”

“…TR34/L98H mutations in the cyp 51A gene were detected in 47.4% of ARA f isolates. However, in 52.6% of phenotypically resistant isolates, no mutations were detected within the cyp 51A gene 51 . Moreover, the prevalence of ARA f in a Danish national surveillance study was 6.1% (66/1083) at patient level and TR 34 /L98H was the most common alteration, but non‐ cyp 51A‐mediated resistance accounted for 19.7% (13/66) 58 .…”

“…33,57 However, in 52.6% of phenotypically resistant isolates, no mutations were detected within the cyp51A gene. 51 Moreover, the prevalence of ARAf in a Danish national surveillance study was 6.1% (66/1083) at patient level and TR 34 /L98H was the most common alteration, but non-cyp51A-mediated resistance accounted for 19.7% (13/66). 58 Strikingly, the majority of studies have shown that over half of the phenotypically resistant isolates harboured no mutations in the cyp51A gene.…”

Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus

“…Much of the current research on azole resistance is focused on the expression or modification of the drug target Cyp51 (Bueid et al, 2010 ; Perez-Cantero et al, 2020 ). Recent estimates for azole resistance displayed that more than 50% of the isolations included non-Cyp51 mutants that exhibit azole resistance for unexplained causes (Ener et al, 2022 ). Hence, additional treatment strategies are necessary for azole resistance to the human fungal pathogen A. fumigatus .…”

The metal chaperone protein MtmA plays important roles in antifungal drug susceptibility in Aspergillus fumigatus

“…Many studies have focused on azole resistance caused by Erg11A mutations and high expression of drug pumps in clinical and environmental settings (Bueid et al, 2010;Perez-Cantero et al, 2020). In recent years, an increasing number of A. fumigatus resistant isolates have been identified for having non-cyp51A mutations but with unexplored verification related to drug resistance (Ener et al, 2022). The integrity of mitochondrial function is an important guarantee of multiple cellular processes (Vakifahmetoglu-Norberg et al, 2017;Akbari et al, 2019;Rossi et al, 2019).…”