Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 11;7(3):205.
doi: 10.3390/jof7030205.

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

Karin Meinike Jørgensen  1 , Marie Helleberg  2 , Rasmus Krøger Hare  1 , Lise Nistrup Jørgensen  3 , Maiken Cavling Arendrup  1   4   5
Affiliations

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

Karin Meinike Jørgensen et al. J Fungi (Basel). .

Abstract

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.

Keywords: A. flavus; A. fumigatus; A. terreus; Aspergillus; azole; environmental resistance; fungicide; resistance.

PubMed Disclaimer

Conflict of interest statement

“The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results”. Outside this work, the authors have the following potential conflicts to declare: M.C.A. has, over the past 5 years, received research grants (paid to the institution) or speaker honoraria (personal fee) from Amplyx, Astellas, Basilea, Cidara, F2G, Gilead, MSD, Novartis, Pfizer, and T2Biosystems. She is the current chairman of the EUCAST-AFST and has previously served on advisory boards for MSD (until 2014) and Pfizer (until 2012). M.H. has, over the past 5 years, received speaker honoraria from GSK, CLS Behring and Gilead and has served on advisory boards for GSK. Gilead and GSK have funded her participation in international scientific meetings and conferences. R.K.H. has over the past 5 years received travel grant and an unrestricted research grant from Gilead. L.N.J. has over the years received research grants (paid to the institution), speaker honoraria (personal fee) and funding for participation in workshops/meetings from BASF, Bayer, Syngenta, Corteva, Adama, Novozymes, UPL, ECOstyle, DLG, Nordic Seed, Sejet, KWS and Globachem K.M.J. has over the past 5 years received travel grants from F2G and Amplyx and a meeting grant from MSD.

References

    1. Lass-Flörl C., Mayr A., Aigner M., Lackner M., Orth-Höller D. A nationwide passive surveillance on fungal infections shows a low burden of azole resistance in molds and yeasts in Tyrol, Austria. Infection. 2018;46:701–704. doi: 10.1007/s15010-018-1170-0. - DOI - PMC - PubMed
    1. Risum M., Hare R.K., Gertsen J.B., Kristensen L., Johansen H.K., Helweg-Larsen J., Abou-Chakra N., Pressler T., Skov M., Jensen-Fangel S., et al. Azole-Resistant Aspergillus fumigatus Among Danish Cystic Fibrosis Patients: Increasing Prevalence and Dominance of TR34/L98H. Front. Microbiol. 2020;11:1850. doi: 10.3389/fmicb.2020.01850. - DOI - PMC - PubMed
    1. Cho S.Y., Lee D.G., Choi J.K., Lee H.J., Kim S.H., Park S.H., Choi S.M., Choi J.H., Yoo J.H., Park Y.J., et al. Characteristics of culture-positive invasive pulmonary aspergillosis in patients with hematologic diseases: Comparison between Aspergillus fumigatus and non-fumigatus Aspergillus species. Medicine. 2017;96:e8841. doi: 10.1097/MD.0000000000008841. - DOI - PMC - PubMed
    1. Klich M.A. Aspergillus flavus: The major producer of aflatoxin. Mol. Plant Pathol. 2007;8:713–722. doi: 10.1111/j.1364-3703.2007.00436.x. - DOI - PubMed
    1. Samson R.A., Peterson S.W., Frisvad J.C., Varga J. New species in Aspergillus section Terrei. Stud. Mycol. 2011;69:39–55. doi: 10.3114/sim.2011.69.04. - DOI - PMC - PubMed

LinkOut - more resources