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Fonsecinone A (<jats:bold>2<\/jats:bold>) exhibited the most potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 4.26, 17.04, and 4.26\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL against ESBL-producing<jats:italic>E. coli, P. aeruginosa<\/jats:italic>, and<jats:italic>E. faecalis<\/jats:italic>, respectively. The inhibitory effects of fonsecinones A (<jats:bold>2<\/jats:bold>) and C (<jats:bold>3<\/jats:bold>) against<jats:italic>E. coli<\/jats:italic>and ESBL-producing<jats:italic>E. coli<\/jats:italic>were comparable to those of amikacin. Molecular docking-based target identification of naphtho-<jats:italic>\u03b3<\/jats:italic>-pyrones<jats:bold>1<\/jats:bold>\u2013<jats:bold>8<\/jats:bold>revealed bacterial enoyl-acyl carrier protein reductase (FabI) as an antibacterial target, which was further validated by FabI affinity and inhibition assays. Fonsecinones A (<jats:bold>2<\/jats:bold>) and C (<jats:bold>3<\/jats:bold>) and aurasperones A (<jats:bold>6<\/jats:bold>) and E (<jats:bold>7<\/jats:bold>) bound FabI specifically and produced concentration-dependent inhibition effects. This work is the first report of anti-drug-resistant bacterial activities of naphtho-<jats:italic>\u03b3<\/jats:italic>-pyrones<jats:bold>1<\/jats:bold>\u2013<jats:bold>8<\/jats:bold>and their possible antibacterial mechanism of action and provides an example of the successful application of<jats:italic>in silico<\/jats:italic>methods for drug target identification and validation and the identification of new lead antibiotic compounds against drug-resistant pathogens.<\/jats:p>","DOI":"10.1038\/srep24291","type":"journal-article","created":{"date-parts":[[2016,4,11]],"date-time":"2016-04-11T09:01:30Z","timestamp":1460365290000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Fungal naphtho-\u03b3-pyrones: Potent antibiotics for drug-resistant microbial pathogens"],"prefix":"10.1038","volume":"6","author":[{"given":"Yan","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xintao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiguang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hucheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangmin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongbo","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,11]]},"reference":[{"key":"BFsrep24291_CR1","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/510477a","volume":"510","author":"MC Djalal","year":"2014","unstructured":"Djalal, M. 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