Fungicides induced triazole-resistance in Aspergillus fumigatus associated with mutations of TR46/Y121F/T289A and its appearance in agricultural fields

Ren, Jie; Jin, Xiangxiang; Zhang, Qian; Zheng, Yuan; Lin, Dunli; Yu, Yunlong

doi:10.1016/j.jhazmat.2016.12.013

Cited by 84 publications

(92 citation statements)

References 43 publications

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“…In addition, a very recent study, clearly highlighted that an acquisition of mutation in the azole target by the environmental strains leads to cross resistance between the azole antifungals in the environment and the clinic (Ren et al, 2017). Among 144 soil samples treated with many azoles (epoxiconazole, tebuconazole, propiconazole, hexaconazole, metconazole), Ren et al found that 5.8% of the analyzed samples were resistant to medical azoles (Ren et al, 2017). Two samples were resistant to voriconazole with most frequent mutations found in the environmental samples (TR46/Y121F/T289A).…”

Section: Link Between Azole Resistance In Agriculture and Clinicmentioning

confidence: 99%

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

et al. 2017

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Agricultural industry uses pesticides to optimize food production for the growing human population. A major issue for crops is fungal phytopathogens, which are treated mainly with azole fungicides. Azoles are also the main medical treatment in the management of Aspergillus diseases caused by ubiquitous fungi, such as Aspergillus fumigatus. However, epidemiological research demonstrated an increasing prevalence of azole-resistant strains in A. fumigatus. The main resistance mechanism is a combination of alterations in the gene cyp51A (TR34/L98H). Surprisingly, this mutation is not only found in patients receiving long-term azole therapy for chronic aspergillosis but also in azole naïve patients. This suggests an environmental route of resistance through the exposure of azole fungicides in agriculture. In this review, we report data from several studies that strongly suggest that agricultural azoles are responsible for medical treatment failure in azole-naïve patients in clinical settings.

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Section: Link Between Azole Resistance In Agriculture and Clinicmentioning

confidence: 99%

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

et al. 2017

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“…These mutations lead to high‐level resistance to triazole antifungals of A fumigatus isolates from both azole‐naive and azole‐treated patients . Furthermore, several institutions report a rise in resistant strains found in environmental niches such as soil samples, paddy fields, aerial samples of hospitals and compost . Compost (decaying plant waste material) is an important source of A fumigatus .…”

Section: Introductionmentioning

confidence: 99%

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

Ahangarkani

Puts

Nabili

et al. 2020

Mycoses

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Background: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. Objective: Screening of environmental presence of azole-resistant A fumigatus in Iran.Methods: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar.Phenotypic MICs were obtained from selected, molecularly confirmed isolates.cyp51A gene sequencing and genotyping of azole-resistant isolates were done.Results: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR 46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype.Conclusion: This is the first report of A fumigatus with TR 46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region. K E Y W O R D SAspergillus fumigatus, azole resistance, compost, TR 34 /L98H, TR46/Y121F/T289A | 431 AHANGARKANI et Al.

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“…A range of MIC 50 values show that there were no differences in resistance factors (= 16) between the two imidazoles and the five triazole DMIs. Attempts to generate TR 34 L98H resistance by in vitro selection were unsuccessful, but a similar resistance combining a promoter insert and point mutations (TR 45 Y1212F/T298A) has since been generated in the laboratory by selection with increasing concentrations of several agricultural fungicides …”

Section: Molecular Interaction Of Azoles With Cyp51amentioning

confidence: 99%

“…Azole‐resistant isolates are certainly present in the environment, but so far there has been little focus on their occurrence in association with crop and animal production systems. A recent Chinese survey of soil samples from 144 greenhouses recovered 73 A. fumigatus isolates, of which two were resistant to voriconazole and one to itraconazole . The authors give no information on cross‐resistance with DMIs, nor do they state if these three isolates were from soils beneath crops treated with agricultural DMIs, which would not necessarily be the fungicides used to control many of the diseases of the 18 different crops involved.…”

Section: Is There a Problem?mentioning

confidence: 99%

“…A recent Chinese survey of soil samples from 144 greenhouses recovered 73 A. fumigatus isolates, of which two were resistant to voriconazole and one to itraconazole. 42 The authors give no information on cross-resistance with DMIs, nor do they state if these three isolates were from soils beneath crops treated with agricultural DMIs, which would not necessarily be the fungicides used to control many of the diseases of the 18 different crops involved. Molecular diagnostics capable of detecting mutations can be applied to DNA from soil or the airspora, in hospital and field environments.…”

Section: Is There a Problem?mentioning

confidence: 99%

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

Hollomon

2017

Pest Management Science

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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.

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Fungicides induced triazole-resistance in Aspergillus fumigatus associated with mutations of TR46/Y121F/T289A and its appearance in agricultural fields

Cited by 84 publications

References 43 publications

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

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

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Fungicides induced triazole-resistance in Aspergillus fumigatus associated with mutations of TR46/Y121F/T289A and its appearance in agricultural fields

Cited by 84 publications

References 43 publications

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR46/Y121F/T289A mutation in Iran

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

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First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran