{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:47:32Z","timestamp":1791557252935,"version":"4.3.4"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T00:00:00Z","timestamp":1433203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A rapid and global emergence of azole resistance has been observed in the pathogenic fungus\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the\n            <jats:italic>cyp51A<\/jats:italic>\n            gene, which encodes a protein targeted by triazole antifungal drugs. Whole-genome sequencing (WGS) was performed for high-resolution single-nucleotide polymorphism (SNP) analysis of 24\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            isolates, including azole-resistant and susceptible clinical and environmental strains obtained from India, the Netherlands, and the United Kingdom, in order to assess the utility of WGS for characterizing the alleles causing resistance. WGS analysis confirmed that TR\n            <jats:sub>34<\/jats:sub>\n            \/L98H (a mutation comprising a tandem repeat [TR] of 34 bases in the promoter of the\n            <jats:italic>cyp51A<\/jats:italic>\n            gene and a leucine-to-histidine change at codon 98) is the sole mechanism of azole resistance among the isolates tested in this panel of isolates. We used population genomic analysis and showed that\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            was panmictic, with as much genetic diversity found within a country as is found between continents. A striking exception to this was shown in India, where isolates are highly related despite being isolated from both clinical and environmental sources across &gt;1,000\u00a0km; this broad occurrence suggests a recent selective sweep of a highly fit genotype that is associated with the TR\n            <jats:sub>34<\/jats:sub>\n            \/L98H allele. We found that these sequenced isolates are all recombining, showing that azole-resistant alleles are segregating into diverse genetic backgrounds. Our analysis delineates the fundamental population genetic parameters that are needed to enable the use of genome-wide association studies to identify the contribution of SNP diversity to the generation and spread of azole resistance in this medically important fungus.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Resistance to azoles in the ubiquitous ascomycete fungus\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            was first reported from clinical isolates collected in the United States during the late 1980s. Over the last decade, an increasing number of\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            isolates from the clinic and from nature have been found to show resistance to azoles, suggesting that resistance is emerging through selection by the widespread usage of agricultural azole antifungal compounds. Aspergillosis is an emerging clinical problem, with high rates of treatment failures necessitating the development of new techniques for surveillance and for determining the genome-wide basis of azole resistance in\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/mbio.00536-15","type":"journal-article","created":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T14:22:37Z","timestamp":1433341357000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":112,"title":["Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing"],"prefix":"10.1128","volume":"6","author":[{"given":"Alireza","family":"Abdolrasouli","sequence":"first","affiliation":[{"name":"National Heart &amp; Lung Institute, Imperial College London, London, United Kingdom"},{"name":"Department of Medical Microbiology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-3187","authenticated-orcid":false,"given":"Mathew A.","family":"Beale","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom"},{"name":"Institute of Infection and Immunity, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferry","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Trinity College Dublin, Dublin, Ireland"},{"name":"St. James\u2019 Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-6080","authenticated-orcid":false,"given":"Jacques F.","family":"Meis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"},{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Armstrong-James","sequence":"additional","affiliation":[{"name":"National Heart &amp; 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