Development of cross-resistance by Aspergillus fumigatus to clinical azoles following exposure to prochloraz, an agricultural azole

The purpose of this study was to unveil whether azole antifungals used in agriculture, similar to the clinical azoles used in humans, can evoke resistance among relevant human pathogens like Aspergillus fumigatus, an ubiquitous agent in nature. Additionally, cross-resistance with clinical azoles was...

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Published in:BMC microbiology 2014-06, Vol.14 (1), p.155-155, Article 155
Main Authors: Faria-Ramos, Isabel, Farinha, Sofia, Neves-Maia, João, Tavares, Pedro Ribeiro, Miranda, Isabel M, Estevinho, Letícia M, Pina-Vaz, Cidália, Rodrigues, Acácio G
Format: Article
Language:English
Subjects:
Agricultural industry
Agriculture
Aspergillosis - microbiology
Aspergillus fumigatus
Aspergillus fumigatus - drug effects
Aspergillus fumigatus - growth & development
Aspergillus fumigatus - isolation & purification
Azoles - pharmacology
Chemical properties
Culture Media - chemistry
Drug resistance in microorganisms
Drug Resistance, Fungal
Environmental Microbiology
Fungicides, Industrial - pharmacology
Growth
Humans
Imidazoles - pharmacology
Microbial Sensitivity Tests
Mutation
R&D
Research & development
Serial Passage
Temperature
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Summary:The purpose of this study was to unveil whether azole antifungals used in agriculture, similar to the clinical azoles used in humans, can evoke resistance among relevant human pathogens like Aspergillus fumigatus, an ubiquitous agent in nature. Additionally, cross-resistance with clinical azoles was investigated. Antifungal susceptibility testing of environmental and clinical isolates of A. fumigatus was performed according to the CLSI M38-A2 protocol. In vitro induction assays were conducted involving daily incubation of susceptible A. fumigatus isolates, at 35°C and 180 rpm, in fresh GYEP broth medium supplemented with Prochloraz (PCZ), a potent agricultural antifungal, for a period of 30 days. Minimal inhibitory concentrations (MIC) of PCZ and clinical azoles were monitored every ten days. In order to assess the stability of the developed MIC, the strains were afterwards sub-cultured for an additional 30 days in the absence of antifungal. Along the in vitro induction process, microscopic and macroscopic cultural observations were registered. MIC of PCZ increased 256 times after the initial exposure; cross-resistance to all tested clinical azoles was observed. The new MIC value of agricultural and of clinical azoles maintained stable in the absence of the selective PCZ pressure. PCZ exposure was also associated to morphological colony changes: macroscopically the colonies became mostly white, losing the typical pigmentation; microscopic examination revealed the absence of conidiation. PCZ exposure induced Aspergillus fumigatus morphological changes and an evident increase of MIC value to PCZ as well as the development of cross-resistance with posaconazole, itraconazole and voriconazole.
ISSN:1471-2180
1471-2180
DOI:10.1186/1471-2180-14-155