Isolation of azole-resistant Aspergillus fumigatus from the environment in the south-eastern USA

Hurst, Steven F.; Berkow, Elizabeth L.; Stevenson, Katherine L.; Litvintseva, Anastasia P.; Lockhart, Shawn R.

doi:10.1093/jac/dkx168

Cited by 66Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Isolation of azole-resistant Aspergillus fumigatus from the environment in the south-eastern USA

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Hurst, Steven F., Berkow, Elizabeth L., Stevenson, Katherine L., Litvintseva, Anastasia P., Lockhart, Shawn R.·2017·Journal of Antimicrobial Chemotherapy

DOI 10.1093/jac/dkx168PMC PMC11935745

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Abstract

Background: Azole resistance in isolates of the fungus Aspergillus fumigatus has been associated with agricultural use of azole fungicides. Environmental isolation of resistant isolates has been reported in Asia, Africa, Europe and South America. Objectives: To determine whether A. fumigatus isolates containing TR34/L98H or TR46/Y121F/T289A can be found in fields in the USA treated with agricultural azoles. Methods: Crop debris was collected and screened for A. fumigatus. All A. fumigatus isolates were screened for azole resistance. The CYP51A gene of azole-resistant isolates was sequenced. The population structure of a subset of isolates was determined using microsatellite typing. Results: This article identifies azole-resistant A. fumigatus isolates containing the TR34/L98H mutation in an experimental peanut field that had been treated with azole fungicides. Conclusions: These findings suggest the development of resistance to azole antifungals in A. fumigatus may be present where agricultural azoles are used in the USA.

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Environmental presence of azole-resistant Aspergillus spp. in places where low socioeconomic populations live, including racial minorities, places those individuals at risk of acquiring invasive disease that is difficult to treat.
“Such environmental presence of azole-resistant Aspergillus spp. in places where low socioeconomic populations live, including racial minorities, places those individuals at risk of acquiring invasive disease that is difficult to treat.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [74]
Azole-resistant Aspergillus spp. is linked to the use of agricultural azoles and has been reported in different parts of the world; incidence in the US remains low, but it was reported from crop debris in the southeast US with isolates carrying TR46/Y121F/T289A mutations linked to azole resistance.
“Lastly, azole-resistant Aspergillus spp. is an emerging pathogen that is linked to the use of agricultural azoles (tebuconazole and propiconazole) has been reported in different parts of the world. The incidence of such azole-resistant Aspergillus spp. in the US remains low, but it was reported from crop debris in the southeast regions of the US, with isolates carrying TR46/Y121F/T289A mutations”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [74]
Duplications in the cyp51A gene promoter coupled with TR34/L98H and TR46/Y121F/T289A substitutions are becoming widespread in the environment associated with azole use in agriculture and are also isolated from hospital patients without previous antifungal exposure.
“Alarmingly, duplications in the cyp51A gene promoter coupled with specific amino acid substitutions, TR34/L98H and TR46/Y121F/T289A, are becoming widespread in the environment associated with azole use in agriculture, while also isolated from hospital patients without previous exposure to antifungal drugs19–22.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [21]

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Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America
Patterson, T. F., Thompson, G. R., Denning, D. W., Fishman, J. A., Hadley, S., Herbrecht, R., Kontoyiannis, D. P., Marr, K. A., Morrison, V. A., Nguyen, M. H., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/ciw326 · Cited by 2,926 · see citing works
eBURST: Inferring Patterns of Evolutionary Descent among Clusters of Related Bacterial Genotypes from Multilocus Sequence Typing Data
Feil, E. J., Li, B. C., Aanensen, D. M., Hanage, W. P., & Spratt, B. G. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.5.1518-1530.2004 · Cited by 1,861 · see citing works
Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant‐Associated Infection Surveillance Network (TRANSNET)
Pappas, P. G., Alexander, B. D., Andes, D. R., Hadley, S., Kauffman, C. A., Freifeld, A., Anaissie, E. J., Brumble, L. M., Herwaldt, L., Ito, J., et al. (2010) · Clinical Infectious Diseases · doi:10.1086/651262 · Cited by 1,570 · see citing works
Emergence of Azole Resistance in Aspergillus fumigatus and Spread of a Single Resistance Mechanism
Snelders, E., van der Lee, H. A. L., Kuijpers, J., Rijs, A. J. M. M., Varga, J., Samson, R. A., Mellado, E., Donders, A. R. T., Melchers, W. J. G., & Verweij, P. E. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050219 · Cited by 726 · see citing works
Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?
Verweij, P. E., Snelders, E., Kema, G. H., Mellado, E., & Melchers, W. J. (2009) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(09)70265-8 · Cited by 604 · see citing works
Azole Resistance in Aspergillus fumigatus : Can We Retain the Clinical Use of Mold-Active Antifungal Azoles?
Verweij, P. E., Chowdhary, A., Melchers, W. J. G., & Meis, J. F. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/civ885 · Cited by 561 · see citing works
A New Aspergillus fumigatus Resistance Mechanism Conferring In Vitro Cross-Resistance to Azole Antifungals Involves a Combination of cyp51A Alterations
Mellado, E., Garcia-Effron, G., Alcázar-Fuoli, L., Melchers, W. J. G., Verweij, P. E., Cuenca-Estrella, M., & Rodríguez-Tudela, J. L. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01092-06 · Cited by 490 · see citing works
Triazole Fungicides Can Induce Cross-Resistance to Medical Triazoles in Aspergillus fumigatus
Snelders, E., Camps, S. M. T., Karawajczyk, A., Schaftenaar, G., Kema, G. H. J., van der Lee, H. A., Klaassen, C. H. W., Melchers, W. J. G., & Verweij, P. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031801 · Cited by 427 · see citing works
Possible Environmental Origin of Resistance of Aspergillus fumigatus to Medical Triazoles
Snelders, E., Huis in 't Veld, R. A. G., Rijs, A. J. M. M., Kema, G. H. J., Melchers, W. J. G., & Verweij, P. E. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.00231-09 · Cited by 423 · see citing works
Multiple-Triazole–Resistant Aspergillosis
Verweij, P. E., Mellado, E., & Melchers, W. J. G. (2007) · New England Journal of Medicine · doi:10.1056/nejmc061720 · Cited by 380 · see citing works
Aspergillosis due to Voriconazole Highly Resistant Aspergillus fumigatus and Recovery of Genetically Related Resistant Isolates From Domiciles
van der Linden, J. W. M., Camps, S. M. T., Kampinga, G. A., Arends, J. P. A., Debets-Ossenkopp, Y. J., Haas, P. J. A., Rijnders, B. J. A., Kuijper, E. J., van Tiel, F. H., Varga, J., et al. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit320 · Cited by 342 · see citing works
International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus
Verweij, P. E., Ananda-Rajah, M. R., Andes, D. R., Arendrup, M. C., Brüggemann, R. J. M., Chowdhary, A., Cornely, O. A., Denning, D. W., Groll, A. H., Izumikawa, K., et al. (2015) · Drug Resistance Updates · doi:10.1016/j.drup.2015.08.001 · Cited by 328 · see citing works
Clinical implications of globally emerging azole resistance in Aspergillus fumigatus
Meis, J. F. G. M., Chowdhary, A., Rhodes, J. L., Fisher, M. C., & Verweij, P. E. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0460 · Cited by 310 · see citing works
Molecular Identification of Aspergillus Species Collected for the Transplant-Associated Infection Surveillance Network
Balajee, S. A., Kano, R., Baddley, J. W., Moser, S. A., Marr, K. A., Alexander, B. D., Andes, D. R., Kontoyiannis, D. P., Perrone, G., Peterson, S., et al. (2009) · Journal of Clinical Microbiology · doi:10.1128/jcm.01070-09 · Cited by 302 · see citing works
Use of a Novel Panel of Nine Short Tandem Repeats for Exact and High-Resolution Fingerprinting of Aspergillus fumigatus Isolates
de Valk, H. A., Meis, J. F. G. M., Curfs-Breuker, I., Muehlethaler, K., Mouton, J. W., & Klaassen, C. H. W. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.8.4112-4120.2005 · Cited by 248 · see citing works
Azole Resistance in Aspergillus fumigatus Isolates from the ARTEMIS Global Surveillance Study Is Primarily Due to the TR/L98H Mutation in the cyp51A Gene
Lockhart, S. R., Frade, J. P., Etienne, K. A., Pfaller, M. A., Diekema, D. J., & Balajee, S. A. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00185-11 · Cited by 232 · see citing works
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Clonal Expansion and Emergence of Environmental Multiple-Triazole-Resistant Aspergillus fumigatus Strains Carrying the TR34/L98H Mutations in the cyp51A Gene in India
Chowdhary, A., Kathuria, S., Xu, J., Sharma, C., Sundar, G., Singh, P. K., Gaur, S. N., Hagen, F., Klaassen, C. H. W., & Meis, J. F. G. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052871 · Cited by 197 · see citing works
Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India
Chowdhary, A., Kathuria, S., Randhawa, H. S., Gaur, S. N. S., Klaassen, C. H. W., & Meis, J. F. G. M. (2011) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkr443 · Cited by 187 · see citing works
Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing
Abdolrasouli, A., Rhodes, J. L., Beale, M. A., Hagen, F., Rogers, T. R., Chowdhary, A., Meis, J. F. G. M., Armstrong-James, D. P. H., & Fisher, M. C. (2015) · mBio · doi:10.1128/mbio.00536-15 · Cited by 177 · see citing works
First Detection of TR34 L98H and TR46 Y121F T289A Cyp51 Mutations in Aspergillus fumigatus Isolates in the United States
Wiederhold, N. P., Gil, V. G., Gutierrez, F., Lindner, J. R., Bataineh, M. T. A., McCarthy, D. I., Sanders, C. J., Fan, H., Fothergill, A. W., & Sutton, D. A. (2015) · Journal of Clinical Microbiology · doi:10.1128/jcm.02478-15 · Cited by 168 · see citing works
Multi-azole-resistant Aspergillus fumigatus in the environment in Tanzania
Chowdhary, A., Sharma, C., van den Boom, M., Yntema, J. B., Hagen, F., Verweij, P. E., & Meis, J. F. G. M. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku259 · Cited by 135 · see citing works
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Bart–Delabesse, E., Humbert, J. F., Delabesse, É., & Bretagne, S. (1998) · Journal of Clinical Microbiology · doi:10.1128/jcm.36.9.2413-2418.1998 · Cited by 134 · see citing works
Azole-resistant Aspergillus fumigatus with the environmental TR46/Y121F/T289A mutation in India
Chowdhary, A., Sharma, C., Kathuria, S., Hagen, F., & Meis, J. F. G. M. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt397 · Cited by 127 · see citing works
Environmental study of azole‐resistant A spergillus fumigatus with TR34/L98H mutations in the cyp51A gene in I ran
Badali, H., Vaezi, A., Haghani, I., Yazdanparast, S. A., Hedayati, M. T., Mousavi, B., Ansari, S., Hagen, F., Meis, J. F. G. M., & Chowdhary, A. (2013) · Mycoses · doi:10.1111/myc.12089 · Cited by 109 · see citing works
Multi‐triazole‐resistant Aspergillus fumigatus infections in Australia
Kidd, S. E., Goeman, E., Meis, J. F. G. M., Slavin, M. A., & Verweij, P. E. (2015) · Mycoses · doi:10.1111/myc.12324 · Cited by 97 · see citing works
Passive Surveillance for Azole-ResistantAspergillus fumigatus, United States, 2011–2013
Pham, C. D., Reiss, E., Hagen, F., Meis, J. F. G. M., & Lockhart, S. R. (2014) · Emerging infectious diseases · doi:10.3201/eid2009.140142 · Cited by 88 · see citing works
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Concomitant occurrence of itraconazole-resistant and -susceptible strains of Aspergillus fumigatus in routine cultures
Ahmad, S., Joseph, L., Hagen, F., Meis, J. F. G. M., & Khan, Z. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku410 · Cited by 62 · see citing works
Multiple Fungicide-Driven Alterations in Azole-ResistantAspergillus fumigatus, Colombia, 2015
Pape, P. L., Lavergne, R., Morio, F., & Álvarez, C. (2015) · Emerging infectious diseases · doi:10.3201/eid2201.150978 · Cited by 54 · see citing works
Voriconazole-Susceptible and Voriconazole-Resistant Aspergillus fumigatus Coinfection
Kolwijck, E., van der Hoeven, H., de Sévaux, R. G. L., ten Oever, J., Rijstenberg, L. L., van der Lee, H. A. L., Zoll, J., Melchers, W. J. G., & Verweij, P. E. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201510-2104le · Cited by 41 · see citing works
Diagnosis and management of aspergillosis in the Netherlands: a national survey
Lestrade, P. P. A., Meis, J. F. G. M., Arends, J. P., van der Beek, M. T., Brauwer, E. D., van Dijk, K., de Greeff, S. C., Haas, P., Hodiamont, C. J., Kuijper, E. J., et al. (2015) · Mycoses · doi:10.1111/myc.12440 · Cited by 40 · see citing works
Molecular Characterization of a Voriconazole-Resistant, Posaconazole-Susceptible Aspergillus fumigatus Isolate in a Lung Transplant Recipient in the United States
Vázquez, J. A., & Manavathu, E. K. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01130-15 · Cited by 34 · see citing works

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Research works printed but not linked: 1

[25]Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi—Second Edition: Approved Standard M38-A2. CLSI, Wayne, PA, USA, 2008. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Reference%20Method%20for%20Broth%20Dilution%20Antifungal%20Susceptibility%20Testing%20of%20Filamentous%20Fungi%E2%80%94Second%20Edition:%20Approved%20Standard%20M38-A2&publication_year=2008&)]

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Mutations in hmg1 , Challenging the Paradigm of Clinical Triazole Resistance in Aspergillus fumigatus
Rybak, J. M., Ge, W., Wiederhold, N. P., Parker, J. E., Kelly, S. L., Rogers, P. D., & Fortwendel, J. R. (2019) · mBio · doi:10.1128/mbio.00437-19 · Cited by 130 · see citing works
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Azole Resistance In Aspergillus Fumigatus : A New Challenge In The Management Of Invasive Aspergillosis?
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Authors: Hurst, S. F., Berkow, E. L., Stevenson, K. L., Litvintseva, A. P., & Lockhart, S. R.
Affiliations: Centers for Disease Control and Prevention (US)
University of Georgia (US)
Corresponding author: Lockhart, Shawn R.
ORCID: Hurst, Steven F.
Berkow, Elizabeth L.
Litvintseva, Anastasia P.
Lockhart, Shawn R.
Venue: Journal of Antimicrobial Chemotherapy
Publisher: Oxford University Press (OUP)
Published: 2017-06-01
Volume: 72
Issue: 9
Pages: 2443-2446
ISSN: 0305-7453 (ISSN-L)
1460-2091
DOI: 10.1093/jac/dkx168
PMC: PMC11935745
OpenAlex: W2621329764
Cited by: 66
References: 31
Citations by year: 2026: 12 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 14 · 2020: 3 · 2019: 7 · 2018: 11 · 2017: 1
FWCI: 4.63
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Antimicrobial Chemotherapy (publishedVersion, public-domain)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: University of Georgia
National Institutes of Health (CC999999)
Centers for Disease Control and Prevention
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Aspergillus fumigatus, azole resistance, TR34/L98H mutation, cyp51A gene, peanut field
MeSH terms: Composting, Antifungal Agents, Aspergillosis, Aspergillus fumigatus, Azoles, Cytochrome P-450 Enzyme System, Fungal Proteins, Fungicides, Industrial, Genotype, Humans, Microbial Sensitivity Tests, Mutation, Soil Microbiology, United States, Crops, Agricultural, Microsatellite Repeats, Drug Resistance, Fungal, High-Throughput Nucleotide Sequencing

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Isolation of azole-resistant Aspergillus fumigatus from the environment in the south-eastern USA

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