Does agricultural use of azole fungicides contribute to resistance in the human pathogen Aspergillus fumigatus?

Abstract

Azole resistance in human fungal pathogens has increased over the past twenty years, especially in immunocompromised patients. Similarities between medical and agricultural azoles, and extensive azole (14α-demethylase inhibitor, DMI) use in crop protection, prompted speculation that resistance in patients with aspergillosis originated in the environment. Aspergillus species, and especially Aspergillus fumigatus, are the largest cause of patient deaths from fungi. Azole levels in soils following crop spraying, and differences in sensitivity between medical and agricultural azoles (DMIs), indicate weaker selection in cropping systems than in patients receiving azole therapy. Most fungi have just one CYP51 paralogue (isozyme CYP51B), but in Aspergillus sp. mutations conferring azole resistance are largely confined to a second paralogue, CYP51A. Binding within the active centre is similar for medical and agricultural azoles but differences elsewhere between the two paralogues may ensure selection depends on the DMI used on crops. Two imidazoles, imazalil and prochloraz, have been widely used since the early 1970s, yet unlike triazoles they have not been linked to resistance in patients. Evidence that DMIs are the origin, or increase the frequency, of azole resistance in human fungal pathogens is lacking. Limiting DMI use would have serious impacts on disease control in many crops, and remove key tools in anti-resistance strategies. © 2017 Society of Chemical Industry.

Elevated MIC Values of Imidazole Drugs against Aspergillus fumigatus Isolates with TR 34 /L98H/S297T/F495I Mutation

“…Over the past few years, evidence for an environmental route of resistance development in A. fumigatus due to applications of azole fungicides in agriculture has been accumulating (9); however, this link has not been proven (19). One of the main arguments has arisen from the lack of evidence of an association between two imidazoles, imazalil and prochloraz, and resistance in patients, although these imidazoles have been widely used since the 1970s (20). Our study clearly demonstrates an association of elevated MIC values of imidazole fungicides with TR 34 /L98H/S297T/F495I mutation in A. fumigatus.…”

Antifungal Agents in Agriculture: Friends and Foes of Public Health

“…However, the excessive use of azoles leads to contamination of soil, air, and plants, mainly because of their lipophilic characteristic, which results in their absorption into soil and organic matter. Azoles exhibit high stability, and can remain virtually unchanged in the environment and in food for months [87,89].…”

RNAi as an emerging approach to control Fusarium head blight disease and mycotoxin contamination in cereals

“…This is preferential, and distinct, to broad‐acting chemical antifungal treatments that promote the evolution of resistance in targeted and non‐targeted fungal populations. One example is the association between the use of azole fungicides in agriculture and the rise of azole‐resistant Aspergillus species in a clinical setting 59. The use of both SIGS and HIGS on a commercial scale appears possible in the near future.…”

“…One example is the association between the use of azole fungicides in agriculture and the rise of azole-resistant Aspergillus species in a clinical setting. 59 The use of both SIGS and HIGS on a commercial scale appears possible in the near future. Similar HIGS-based approaches developed to control FHB in wheat may be developed and assessed for their efficacy to control other Fusarium-incited diseases of other important crops, e.g.…”