Mutation in cyp51A and high expression of efflux pump gene of Aspergillus fumigatus induced by propiconazole in liquid medium and soil

Cao, Duantao; Yao, Shijie; Zhang, Hongchao; Wang, Saige; Jin, Xiangxiang; Lin, Dunli; Fang, Hua; Yu, Yunlong

doi:10.1016/j.envpol.2019.113385

Cited by 12 publications

(14 citation statements)

References 45 publications

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“…Alteration to these residues has been reported to be associated with azole resistance in A. fumigatus (18). Amino acid substitutions G138S, M220I, and T289A of Cyp51A have been reported to be associated with azole resistance in A. fumigatus, with T289A/Y121F/TR 46 being the most common azole resistance-related genotype (22,32). The T440A mutation was noted in our study.…”

Section: Discussionsupporting

confidence: 64%

“…Notably, the L. prolificans Cyp51 protein contained residues at three locations (S153, I235, and A302) that corresponded to three residues (G138, M220, and T289) in A. fumigatus Cyp51A (Fig. 1B) whose alterations (G138S, M220I, and T289A) have been reported to be associated with azole resistance (22)(23)(24). These innate or intrinsic amino acid residues presented in L. prolificans at the above locations corresponded to respective mutations found in azole-resistant A. fumigatus Cyp51A.…”

Section: Resultsmentioning

confidence: 97%

“…Although such a mutation associated with azole resistance in Aspergillus was suggested previously (33), there was no molecular data to support this notion. While the G138C was previously indicated (34), the association of G138S with azole resistance in A. fumigatus was recently reported (22). M220 substitutions conferred high itraconazole MIC and elevated MICs for the other azoles in A. fumigatus (24).…”

Section: Discussionmentioning

confidence: 94%

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Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates

Grossman

Totten

et al. 2020

Antimicrob Agents Chemother

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Lomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here we tested the in vitro susceptibility of eight drugs against 42 clinical L. prolificans isolates. All isolates showed high minimal inhibitory concentrations (MICs) to voriconazole (MIC90>16 μg/ml), itraconazole (MIC90>16 μg/ml), posaconazole (MIC90>16 μg/ml), isavuconazole (MIC90>16 μg/ml), amphotericin B (MIC90>16 μg/ml), terbinafine (MIC90>64 μg/ml), and high minimum effective concentration (MEC) to micafungin (MEC90>8 μg/ml), with the exception for miltefosine showing an MIC90 value of 4 μg/ml. We examined six different in vitro drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against L. prolificans. We then annotated L. prolificans whole genome and located its Cyp51 and Fks1 genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in L. prolificans. We found no amino acid changes in Cyp51 protein and no tandem repeats in 5′ upstream region of the Cyp51 gene. However, we identified three intrinsic amino acid residues (G138S, M220I, T289A) in Cyp51 protein that were linked to azole resistance. Likewise, two intrinsic amino acid residues (F639Y, W695F) that have reported to confer echinocandin resistance were found in Fks1 hot spot regions. In addition, three new amino acid alterations (D440A, S634R and H1245R) were found outside of Fks1 hot spot regions and their contributions to echinocandin resistance needs future investigation. Overall, our findings support the notion that L. prolificans is intrinsically resistant to azoles and echinocandins.

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Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 94%

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Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates

Grossman

Totten

et al. 2020

Antimicrob Agents Chemother

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“…To explore the underlying mutations of isolated non-WT A. fumigatus, the cyp51A and promoter regions were amplified and sequenced according to the method proposed by Ren et al (6). For the non-WT strain without mutation, the mRNA expression levels of cyp51 (cyp51A and cyp51B) and two transporters (AfuMDR3 and AfuMDR4) were assessed according to the methods described by Cao et al (16). The results were analyzed according to the 2 ϪooCT method (17).…”

mentioning

confidence: 99%

Five-Year Survey (2014 to 2018) of Azole Resistance in Environmental Aspergillus fumigatus Isolates from China

Cao

Dong

et al. 2020

Antimicrob Agents Chemother

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A total of 191 soil samples from Hangzhou, China, were submitted to detect non-wild-type (non-WT) Aspergillus fumigatus and its associated mechanisms. There were 2 (4.7%), 13 (12.4%), and 31 (23.1%) isolates identified as non-WT in 2014, 2016, and 2018, respectively. The resistant mutations of TR34/L98H, TR46/Y121F/T289A, and TR34/L98H/S297T/F495I were found in 3, 5, and 5 non-WT isolates. The G448S mutation, previously only found in clinical settings, was detected in A. fumigatus from soil samples.

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“…The presence of the same mutation in environmental isolates [92,101,142], the genetic similarity between clinical and environmental isolates [118,138,139,143], the global spread of these mutations [92,94,96,101,144,145] and most recently, studies showing the lower diversity present in resistant strains with these mutations in relation to wild type strains [107,146] support this hypothesis. Since then, several studies have shown the role of azole pesticides used in agriculture in the selection of resistant strains of A. fumigatus [92,117,142,147,148].…”

Section: The Role Of Pesticides In Emerging Aspergillus Azole Resistancementioning

confidence: 99%

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance

et al. 2020

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The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, in view of their ubiquity, as well as their importance as plant pathogens, and potentially fatal pathogens for, particularly, humans and avian species. In addition, the emergence of azole resistance, mainly in Aspergillus fumigatus sensu stricto, and the proven role of fungicides widely used on crops, reinforces the need for a multidisciplinary approach to this problem. Avian species are involved in short and long distance travel between different types of landscapes, such as agricultural fields, natural environments and urban environments. Thus, birds can play an important role in the dispersion of Aspergillus, and of special concern, azole-resistant strains. In addition, some bird species are particularly susceptible to aspergillosis. Therefore, avian aspergillosis could be considered as an environmental health indicator. In this review, aspergillosis in humans and birds will be discussed, with focus on the presence of Aspergillus in the environment. We will relate these issues with the emergence of azole resistance on Aspergillus. These topics will be therefore considered and reviewed from the “One Health” perspective.

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Mutation in cyp51A and high expression of efflux pump gene of Aspergillus fumigatus induced by propiconazole in liquid medium and soil

Cited by 12 publications

References 45 publications

Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates

Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates

Five-Year Survey (2014 to 2018) of Azole Resistance in Environmental Aspergillus fumigatus Isolates from China

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance

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