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Review
. 2013 Oct;9(10):e1003633.
doi: 10.1371/journal.ppat.1003633. Epub 2013 Oct 24.

Emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health

Anuradha Chowdhary  1 , Shallu Kathuria, Jianping Xu, Jacques F Meis
Affiliations
Review

Emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health

Anuradha Chowdhary et al. PLoS Pathog. 2013 Oct.

Erratum in

  • PLoS Pathog. 2013 Nov;9(11). doi:10.1371/annotation/4ffcf1da-b180-4149-834c-9c723c5dbf9b
No abstract available

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Conflict of interest statement

JFM received grants from Astellas, Basilea, and Merck. He has been a consultant to Astellas, Basilea, and Merck and received speaker's fees from Merck and Gilead. All other authors have declared that no competing interests exist. This does not alter our adherence to all PLOS Pathogens policies on sharing data and materials.

Figures

Figure 1
Figure 1. Diagrammatic representation of similar structural binding mode of medical triazoles and triazole fungicides to cyp51A of wild-type A. fumigatus.
(a) Dihalogenated phenyl group of triazoles forms van der Waals contact with the hydrophobic residues (encircled in red) of the active site (cyp51A), and the nitrogen atom of the five-membered aromatic ring of triazoles binds to the cyp51A heme moiety. In addition, the D-ring propionate (C2H5COO−) of the heme moeity forms hydrogen bonds with the side-chain hydroxyl group of triazoles. (b) Triazole fungicides show similar van der Waals contact at the hydrophobic pocket. However, the nitrogen atom of the five-membered aromatic ring of fungicide triazoles binds to the Ser297 residue at the active site. In addition, the triazoles tebuconazole and epoxiconazole are known to interact with the His296 residue while penconazole and metconazole form water-bridging interactions at the active site.
Figure 2
Figure 2. A global map depicting geographic distribution of multi-triazole-resistant clinical (red) and environmental (green) Aspergillus fumigatus strains carrying the TR34/L98H (circle) and the TR46/Y121F/T289A mutations (square).
Countrywide prevalence rates (%) of A. fumigatus carrying TR34/L98H are presented excepting the United Kingdom, where overall azole resistance is illustrated. The percent in parentheses denotes environmental prevalence rates.
See this image and copyright information in PMC

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