{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:03:02Z","timestamp":1785801782693,"version":"3.56.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","award":["F.2-15\/2003 SA-I"],"award-info":[{"award-number":["F.2-15\/2003 SA-I"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Invasive and allergic infections by\n            <jats:named-content content-type=\"genus-species\">Aspergillus flavus<\/jats:named-content>\n            are more common in tropical and subtropical countries. The emergence of voriconazole (VRC) resistance in\n            <jats:named-content content-type=\"genus-species\">A. flavus<\/jats:named-content>\n            impacts the management of aspergillosis, as azoles are used as the first-line and empirical therapy. We screened 120 molecularly confirmed\n            <jats:named-content content-type=\"genus-species\">A. flavus<\/jats:named-content>\n            isolates obtained from respiratory and sinonasal specimens in a chest hospital in Delhi, India, for azole resistance using the CLSI broth microdilution (CLSI-BMD) method. Overall, 2.5% (\n            <jats:italic>n<\/jats:italic>\n            = 3\/120) of\n            <jats:named-content content-type=\"genus-species\">A. flavus<\/jats:named-content>\n            isolates had VRC MICs above epidemiological cutoff values (&gt;1 \u03bcg\/ml). The whole-genome sequence analysis of three non-wild-type (WT)\n            <jats:named-content content-type=\"genus-species\">A. flavus<\/jats:named-content>\n            isolates with high VRC MICs showed polymorphisms in azole target genes (\n            <jats:italic>cyp51A<\/jats:italic>\n            ,\n            <jats:italic>cyp51B<\/jats:italic>\n            , and\n            <jats:italic>cyp51C<\/jats:italic>\n            ). Further, four novel substitutions (S196F, A324P, N423D, and V465M) encoded in the\n            <jats:italic>cyp51C<\/jats:italic>\n            gene were found in a single non-WT isolate which also exhibited overexpression of\n            <jats:italic>cyp51<\/jats:italic>\n            (\n            <jats:italic>cyp51A<\/jats:italic>\n            , -\n            <jats:italic>B<\/jats:italic>\n            , and -\n            <jats:italic>C<\/jats:italic>\n            ) genes and transporter genes, namely,\n            <jats:italic>MDR1<\/jats:italic>\n            ,\n            <jats:italic>MDR2<\/jats:italic>\n            ,\n            <jats:italic>atrF<\/jats:italic>\n            , and\n            <jats:italic>mfs1<\/jats:italic>\n            . The homology model of the non-WT isolate suggests that substitutions S196F and N423D exhibited major structural and functional effects on cyp51C drug binding. The substrate (drug) may not be able to bind to binding pocket due to changes in the pocket size or closing down or narrowing of cavities in drug entry channels. Notably, the remaining two VRC-resistant\n            <jats:named-content content-type=\"genus-species\">A. flavus<\/jats:named-content>\n            isolates, including the one which had a pan-azole resistance phenotype (itraconazole and posaconazole), did not show upregulation of any of the analyzed target genes. These results suggest that multiple target genes and mechanisms could simultaneously contribute to azole resistance in\n            <jats:named-content content-type=\"genus-species\">A. flavus<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.01928-17","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T11:55:46Z","timestamp":1515498946000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Investigation of Multiple Resistance Mechanisms in Voriconazole-Resistant Aspergillus flavus Clinical Isolates from a Chest Hospital Surveillance in Delhi, India"],"prefix":"10.1128","volume":"62","author":[{"given":"Cheshta","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Translational Bioinformatics Group, International Center for Genetic Engineering and Biotechnology, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Kumar","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aradhana","family":"Masih","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Translational Bioinformatics Group, International Center for Genetic Engineering and Biotechnology, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-7462","authenticated-orcid":false,"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"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206291"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780400020113"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/007641-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780802247702"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/651263"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00383-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00233-15"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.1997.tb00217.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12314"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw326"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix210"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ885"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05477-11"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2013.04.022"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00637-15"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.5812\/jjm.26990"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.15171\/apb.2017.007"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(97)00281-3"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.06.018"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/15572536.2006.11832738"},{"key":"e_1_3_2_22_2","volume-title":"CLSI document M38-A2","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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