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

Martyna Mroczyńska,Marta Adamik,Ewelina Kurzyk,Anna Brillowska-Dąbrowska,Urszula Nawrot,Magdalena Śliwka-Kaszyńska

doi:10.3390/microorganisms8020285

Martyna Mroczyńska, Marta Adamik + Show 4 more

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https://doi.org/10.3390/microorganisms8020285

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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.

Highlights

Aspergillus fumigatus is a saprophytic mold widespread in the environment
Summing up the gene expression patterns in isolates grown with the addition of different azoles, we found that all of the studied azoles (POS, VOR and ITR) caused a significant increase in expression of the cyp51A and atrF genes of all tested A. fumigatus isolates
Consistent with our findings, a significant minimal inhibitory concentration (MIC) increase was noted in all examined strains

Summary

Introduction

Aspergillus fumigatus is a saprophytic mold widespread in the environment. It lives among dead and decaying organic matter in the soil and plays an important role in carbon and nitrogen biogeochemical cycles [1]. A. fumigatus is an opportunistic microorganism that threatens immunocompromised patients. It is the most common clinical cause of a group of illnesses collectively called aspergillosis. These diseases manifest as allergy, colonization or invasive infection [2]. The mortality rate caused by A. fumigatus ranges from 30% to 90% in patients with the highest risk (e.g., those immunocompromised by HIV/AIDS) [5,7,8,9]

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