title: Environmental azole fungicide, prochloraz, can induce cross-resistance to medical triazoles in Candida glabrata.
abstract: Acquisition of azole resistance by clinically relevant yeasts in nature may result in a significant, yet undetermined, impact in human health. The main goal of this study was to assess the development of cross-resistance between agricultural and clinical azoles by Candida spp. An in vitro induction assay was performed, for a period of 90 days, with prochloraz (PCZ) - an agricultural antifungal. Afterward, the induced molecular resistance mechanisms were unveiled. MIC value of PCZ increased significantly in all Candida spp. isolates. However, only C. glabrata developed cross-resistance to fluconazole and posaconazole. The increased MIC values were stable. Candida glabrata azole resistance acquisition triggered by PCZ exposure involved the upregulation of the ATP binding cassette multidrug transporter genes and the transcription factor, PDR1. Single mutation previously implicated in azole resistance was found in PDR1 while ERG11 showed several synonymous single nucleotide polymorphisms. These results might explain why C. glabrata is so commonly less susceptible to clinical azoles, suggesting that its exposure to agricultural azole antifungals may be associated to the emergence of cross-resistance. Such studies forward potential explanations for the worldwide increasing clinical prevalence of C. glabrata and the associated worse prognosis of an infection by this species.
authors.affiliation: Microbiology Department, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Faria-Ramos
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Tavares
authors.forename: Sofia
authors.initials: S
authors.lastname: Farinha
authors.forename: João
authors.initials: J
authors.lastname: Neves-Maia
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Miranda
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Silva
authors.forename: Letícia M
authors.initials: LM
authors.lastname: Estevinho
authors.forename: Cidalia
authors.initials: C
authors.lastname: Pina-Vaz
authors.forename: Acácio G
authors.initials: AG
authors.lastname: Rodrigues
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D005659:Fungicides, Industrial; D007093:Imidazoles; D014157:Transcription Factors; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System; C045362:prochloraz
keywords: Candida glabrata; agriculture; clinical resistance