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Cross‐resistance to fluconazole induced by exposure to the agricultural azole tetraconazole: an environmental resistance school?

2016; Wiley; Volume: 59; Issue: 5 Linguagem: Inglês

10.1111/myc.12457

1439-0507

Marcos Fábio Gadelha Rocha, Lucas Pereira de Alencar, Manoel de Araújo Neto Paiva, Luciana Magalhães Melo, Silviane Praciano Bandeira, Yago Brito de Ponte, Jamille Alencar Sales, Gláucia M.M. Guedes, Débora de Souza Collares Maia Castelo‐Branco, Tereza J. P. G. Bandeira, Rossana de Aguiar Cordeiro, Waldemiro Aquino Pereira-Neto, G. S. Brandine, José Luciano Bezerra Moreira, José Júlio Costa Sidrim, Raimunda Sâmia Nogueira Brilhante,

Helminth infection and control

Summary This study aimed to investigate the influence of tetraconazole and malathion, both used in agricultural activities, on resistance to fluconazole, itraconazole and voriconazole in Candida parapsilosis ATCC 22019. The susceptibility to tetraconazole, malathion, fluconazole, itraconazole and voriconazole, through broth microdilution. Then, 12 independent replicates, were separated and exposed to four treatment groups, each one containing three replicates: G1: tetraconazole; G2: malathion; G3: fluconazole (positive control); G4: negative control. Replicates from G1, G2 and G3, were exposed to weekly increasing concentrations of tetraconazole, malathion and fluconazole, respectively, ranging from MIC/2 to 32 × MIC, throughout 7 weeks. The exposure to tetraconazole, but not malathion, decreased susceptibility to clinical azoles, especially fluconazole. The tetraconazole‐induced fluconazole resistance is partially mediated by the increased activity of ATP‐dependent efflux pumps, considering the increase in antifungal susceptibility after the addition of the efflux pump inhibitor, promethazine, and the increase in rhodamine 6G efflux and CDR gene expression in the G1 replicates. Moreover, MDR expression was only detected in G1 and G3 replicates, suggesting that MDR pumps are also involved in tetraconazole‐induced fluconazole resistance. It is noteworthy that tetraconazole and fluconazole‐treated replicates behaved similarly, therefore, resistance to azoles of clinical use may be a consequence of using azoles in farming activities.