The Effect of Posaconazole, Itraconazole and Voriconazole in the Culture Medium on Aspergillus fumigatus Triazole Resistance

Abstract

Triazoles are the only compounds used as antibiotics in both medicine and agriculture. The presence of triazoles in the environment can contribute to the acquisition of azole resistance among isolates of Aspergillus fumigatus. The objective of this study was to investigate the effect of A. fumigatus exposure to triazoles on susceptibility to these compounds. Seventeen triazole-resistant and 21 triazole-sensitive A. fumigatus isolates were examined. The isolates were transferred 20 times on the Sabouraud medium supplemented with posaconazole, itraconazole or voriconazole, followed by five times on the medium not supplemented. The minimum inhibitory concentrations of antimycotics were examined according to the EUCAST broth microdilution method after the 20th transfer and also the 25th transfer. In addition, the expression levels of genes mdr1, mdr2, mdr3, atrF, cyp51A and cyp51B were determined. Cultivation of A. fumigatus on media supplemented with posaconazole, itraconazole and voriconazole resulted in the acquisition of resistance to the tested triazoles of all examined isolates. After recultivation on Sabouraud without azoles, most of the isolates lost their acquired resistance. The long-term use of triazole compounds in agriculture may result in the occurrence of triazole resistant A. fumigatus isolates in the environment, not only by induction or selection of mutations in the cyp51A gene, but also by contribution to changes in the gene expression.

Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2

“…The closest TruMDR2 homologue of A. fumigatus is mdr1/AFUA5G06070 (68.5% identity over a range of 1331 amino acids) (Figure 4). A. fumigatus mdr1 is induced by VRC, 20 and its expression is also affected by other azoles 21 . Disruption of the mdr1 gene showed a twofold decrease in the MIC of ITC, VRC and posaconazole (POS) 22 .…”

“…A. fumigatus mdr1 is induced by VRC, 20 and its expression is also affected by other azoles. 21 Disruption of the mdr1 gene showed a twofold decrease in the MIC of ITC, VRC and posaconazole (POS). 22 In addition, it has been shown to confer resistance to cilofungin when heterologously expressed in S cerevisiae, confirming a putative role in drug resistance.…”