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

Cao, Duantao; Wu, Ruilin; Dong, Suxia; Wang, Feiyan; Ju, Chao; Song, Yu; Xu, Shiji; Fang, Hua; Yu, Yunlong

doi:10.1128/aac.00904-20

Cited by 16 publications

(24 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, it has become clear that several point mutations causing azole resistance can also be found in environmental isolates. For example, A. fumigatus isolates harbouring single point target gene mutations have been found in the environment including G54A in Germany [ 39 ], G54E in Italy, India, Romania, Tanzania, and Argentina [ 40 , 41 , 42 , 43 ], G54R in Switzerland and Thailand [ 44 , 45 ], M220I in Germany [ 39 ], P216L and H285Y in France [ 46 , 47 ], and G448S in China [ 48 ]. Moreover, clinical A. flavus isolates harbouring point mutations conferring Cyp51A P214L (itraconazole and posaconazole resistant) or Cyp51C H349R (pan human azole resistant) alterations displayed cross resistance to imazalil, prochloraz, metconazole, tebuconazole, epoxiconazole, and bromuconazole [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Dissection of the Activity of Agricultural Fungicides against Clinical Aspergillus Isolates with and without Environmentally and Medically Induced Azole Resistance

Jørgensen

Helleberg

Hare

et al. 2021

JoF

View full text Add to dashboard Cite

Azole resistance is an emerging problem in patients with aspergillosis. The role of fungicides for resistance development and occurrence is not fully elucidated. EUCAST reference MICs of 17 fungicides (11 azoles and 6 others), five azole fungicide metabolites and four medical triazoles were examined against two reference and 28 clinical isolates of A. fumigatus, A. flavus and A. terreus with (n = 12) and without (n = 16) resistance mutations. Eight/11 azole fungicides were active against wild-type A. fumigatus, A. flavus and A. terreus, including four (metconazole, prothioconazole-desthio, prochloraz and imazalil) with low MIC50 (≤2 mg/L) against all three species and epoxiconazole, propiconazole, tebuconazole and difenoconazole also against wild-type A. terreus. Mefentrifluconazole, azole metabolites and non-azole fungicides MICs were >16 mg/L against A. fumigatus although partial growth inhibition was found with mefentrifluconazole. Moreover, mefentrifluconazole and axozystrobin were active against wild-type A. terreus. Increased MICs (≥3 dilutions) were found for TR34/L98H, TR34(3)/L98H, TR46/Y121F/T289A and G432S compared to wild-type A. fumigatus for epoxiconazole, propiconazole, tebuconazole, difenoconazole, prochloraz, imazalil and metconazole (except G432S), and for prothioconazole-desthio against TR46/Y121F/T289A, specifically. Increased MICs were found in A. fumigatus harbouring G54R, M220K and M220R alterations for five, one and one azole fungicides, respectively, compared to MICs against wild-type A. fumigatus. Similarly, increased MICs wer found for A. terreus with G51A, M217I and Y491H alterations for five, six and two azole fungicides, respectively. Azole fungicides showed activity against wild-type A. fumigatus, A. terreus and A. flavus, but not against all mutant isolates, suggesting the environmental route of azole resistance may have a role for all three species.

show abstract

Section: Discussionmentioning

confidence: 99%

Dissection of the Activity of Agricultural Fungicides against Clinical Aspergillus Isolates with and without Environmentally and Medically Induced Azole Resistance

Jørgensen

Helleberg

Hare

et al. 2021

JoF

View full text Add to dashboard Cite

show abstract

“…Fungi with acquired azole resistance are likely to have a fitness advantage in azole-contaminated environments [ 18 , 133 , 134 , 135 , 136 , 137 ]. In addition, fungi such as mucormycetes that are intrinsically resistant to short-tailed azoles should benefit from a positive selection pressure in azole-rich environments and outcompete azole-susceptible species [ 137 ].…”

Section: Discussionmentioning

confidence: 99%

Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens

Rosam

Monk

Lackner

2020

JoF

View full text Add to dashboard Cite

The fungal cytochrome P450 enzyme sterol 14α-demethylase (SDM) is a key enzyme in the ergosterol biosynthesis pathway. The binding of azoles to the active site of SDM results in a depletion of ergosterol, the accumulation of toxic intermediates and growth inhibition. The prevalence of azole-resistant strains and fungi is increasing in both agriculture and medicine. This can lead to major yield loss during food production and therapeutic failure in medical settings. Diverse mechanisms are responsible for azole resistance. They include amino acid (AA) substitutions in SDM and overexpression of SDM and/or efflux pumps. This review considers AA affecting the ligand-binding pocket of SDMs with a primary focus on substitutions that affect interactions between the active site and the substrate and inhibitory ligands. Some of these interactions are particularly important for the binding of short-tailed azoles (e.g., voriconazole). We highlight the occurrence throughout the fungal kingdom of some key AA substitutions. Elucidation of the role of these AAs and their substitutions may assist drug design in overcoming some common forms of innate and acquired azole resistance.

show abstract

“…TR 34 /L98H is a typical TR-type mutation conferring resistance to ITCZ and in some cases to VRCZ, whereas TR 46 /Y121F/T289A confers resistance to VRCZ and in most cases to ITCZ (van Ingen et al, 2015, Buil et al, 2018). Amino acid substitution G448S contributes to resistance to VRCZ and occasionally to ITCZ (Bellete et al, 2010, Toyotome et al, 2016, Cao et al, 2020). Our finding that three strains (3-1-B, 3-1-C, and 3-1-D) showed a higher tolerance to VRCZ and some DMIs than strains with only TR 46 /Y121F/T289A mutation is suggestive of elevation of tolerance to azole drugs by combining mutations.…”

Section: Discussionmentioning

confidence: 99%

“…TR-type mutant strains were spread worldwide. Some isolates from multiple countries were genetically closely related to each other and some had identical microsatellite patterns (Pontes et al, 2020, Cao et al, 2020, Wang et al, 2018, Hagiwara et al, 2016b). Besides such international propagation, intranational clonal expansion was also reported in several countries (Ahangarkani et al, 2020, Chowdhary et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Intimate genetic relationships and fungicide resistance in multiple strains of human pathogenic fungus Aspergillus fumigatus isolated from a plant bulb

Takahashi

Oiki

Kusuya

et al. 2021

Preprint

View full text Add to dashboard Cite

Fungal infections are increasingly dangerous because of environmentally-dispersed resistance to antifungal drugs. Azoles are commonly used antifungal drugs, but they are also used as fungicides in agriculture, which may enable enrichment of azole-resistant strains of the human pathogen Aspergillus fumigatus in the environment. Understanding of environmental dissemination and enrichment of genetic variation associated with azole resistance in A. fumigatus is required to suppress resistant strains. Here, we focused on eight strains of azole-resistant A. fumigatus isolated from a single tulip bulb for sale in Japan. This set includes strains with TR34/L98H/T289A/I364V/G448S and TR46/Y121F/T289A/S363P/I364V/G448S mutations in the cyp51A gene, which showed higher tolerance to several azoles than strains harboring TR46/Y121F/T289A mutation. The strains were typed by microsatellite typing, single nucleotide polymorphism profiles, and mitochondrial and nuclear genome analyses. The strains grouped differently using each typing method, suggesting historical genetic recombination among the strains. Our data also revealed that some strains isolated from the tulip bulb showed tolerance to other classes of fungicide, such as QoI and carbendazim, followed by related amino acid alterations in the target proteins. Considering spatial-temporal factors, plant bulbs are an excellent environmental niche for fungal strains to encounter partners, and to obtain and spread resistance-associated mutations.

show abstract

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

Cited by 16 publications

References 33 publications

Dissection of the Activity of Agricultural Fungicides against Clinical Aspergillus Isolates with and without Environmentally and Medically Induced Azole Resistance

Dissection of the Activity of Agricultural Fungicides against Clinical Aspergillus Isolates with and without Environmentally and Medically Induced Azole Resistance

Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens

Intimate genetic relationships and fungicide resistance in multiple strains of human pathogenic fungus Aspergillus fumigatus isolated from a plant bulb

Contact Info

Product

Resources

About