Analysis of Cyp51 protein sequences shows 4 major Cyp51 gene family groups across Fungi

Celia-Sanchez, Brandi N.; Mangum, Brandon; Brewer, Marin Talbot; Momany, Michelle

doi:10.1101/2022.05.18.492509

Cited by 2 publications

(1 citation statement)

References 48 publications

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“…Azoles are also widely used as agricultural fungicides to combat fungal pathogens of crops (4). Azoles target a conserved Cyp51 protein (also known as Cyp51A, Cyp51B, ERG11) in the pathway that makes ergosterol, a fungal sterol responsible for cell membrane fluidity (5). Binding of azoles to Cyp51 causes arrested growth, toxic sterol intermediates, and fungal cell death (6).…”

Section: Introductionmentioning

confidence: 99%

Pan-azole- and multi-fungicide-resistantAspergillus fumigatusis widespread in the United States

Celia-Sanchez,

Mangum,

Gómez Londoño

et al. 2023

Preprint

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Aspergillus fumigatusis an important global fungal pathogen of humans. Azole drugs are among the most effective treatments forA. fumigatusinfection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistantA. fumigatushas been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance inA. fumigatusare tandem repeats (TR) in thecyp51Apromoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistantA. fumigatushas been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistantA. fumigatusin the U.S., we collected isolates from agricultural sites in 8 states and tested 202 isolates for sensitivity to azoles. We found azole-resistantA. fumigatusin agricultural environments in 7 states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades and that TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow with clear recombination between two clades highlighting the potential for azole-resistance to continue spreading in the U.S.ImportanceAspergillus fumigatusis a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris and compost. Azoles are the first line of defense antifungal drugs againstA. fumigatus. Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistantA. fumigatushas been a problem in Europe and Asia for twenty years and has recently been reported in patients in the U.S. Until this study we didn’t know much about azole-resistantA. fumigatusin agricultural settings in the U.S. In this study we isolated azole-resistantA. fumigatusfrom multiple states and compared it to isolates from around the world. We show thatA. fumigatusthat is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S.

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Section: Introductionmentioning

confidence: 99%

Pan-azole- and multi-fungicide-resistantAspergillus fumigatusis widespread in the United States

Celia-Sanchez,

Mangum,

Gómez Londoño

et al. 2023

Preprint

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In Vitro Evaluation of Azoxystrobin, Boscalid, Fentin-Hydroxide, Propiconazole, Pyraclostrobin Fungicides against Alternaria alternata Pathogen Isolated from Carya illinoinensis in South Africa

et al. 2023

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Black spot disease or Alternaria black spot (ABS) of pecan (Carya illinoinensis) in South Africa is caused by Alternaria alternata. This fungal pathogen impedes the development of pecan trees and leads to low yield in pecan nut production. The present study investigated the in vitro effect of six fungicides against the mycelial growth of A. alternata isolates from ABS symptoms. Fungicides tested include Tilt (propiconazole), Ortiva (azoxystrobin), AgTin (fentin hydroxide), and Bellis (boscalid + pyraclostrobin). All fungicides were applied in 3 concentrations (0.2, 1, and 5 μg mL−1). Tilt and Bumper 250 EC containing propiconazole active ingredient (demethylation Inhibitors) were the most effective and inhibited all mycelial growth from up to 6 days post-incubation. The other active ingredients (succinate dehydrogenase inhibitors, organotin compounds, and quinone outside inhibitors) showed 75–85% mycelial growth inhibition. The effective concentration to inhibit mycelial growth by 50% (EC50) was estimated for each isolate and fungicide. The overall mean EC50 values for each fungicide on the six isolates were 1.90 μg mL−1 (Tilt), 1.86 μg mL−1 (Ortiva), 1.53 μg mL−1 (AgTin), and 1.57 μg mL−1 for (Bellis). This initial screening suggested that propiconazole fungicide was the most effective for future field trials test and how these fungicides could be used in controlling ABS disease.

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Analysis of Cyp51 protein sequences shows 4 major Cyp51 gene family groups across Fungi

Cited by 2 publications

References 48 publications

Pan-azole- and multi-fungicide-resistantAspergillus fumigatusis widespread in the United States

Pan-azole- and multi-fungicide-resistantAspergillus fumigatusis widespread in the United States

In Vitro Evaluation of Azoxystrobin, Boscalid, Fentin-Hydroxide, Propiconazole, Pyraclostrobin Fungicides against Alternaria alternata Pathogen Isolated from Carya illinoinensis in South Africa

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