{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:42:50Z","timestamp":1791434570821,"version":"4.3.3"},"reference-count":48,"publisher":"Microbiology Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,5,1]]},"abstract":"<jats:p>Acetolactate synthase catalyses the first common step in isoleucine and valine biosynthesis and is the target of several classes of inhibitors. The<jats:italic>Cryptococcus neoformans ILV2<\/jats:italic>gene, encoding acetolactate synthase, was identified by complementation of a<jats:italic>Saccharomyces cerevisiae ilv2<\/jats:italic>mutant.<jats:italic>C. neoformans<\/jats:italic>is highly resistant to the commercially available acetolactate synthase inhibitor, sulfometuron methyl (SM). Expression of<jats:italic>C. neoformans ILV2<\/jats:italic>in<jats:italic>S. cerevisiae<\/jats:italic>conferred SM resistance, indicating that the SM resistance of<jats:italic>C. neoformans<\/jats:italic>is due, at least in part, to<jats:italic>C. neoformans<\/jats:italic>Ilv2p. The<jats:italic>C. neoformans ILV2<\/jats:italic>gene was disrupted. The<jats:italic>ilv2<\/jats:italic>mutants were auxotrophic for isoleucine and valine and the auxotrophy was satisfied by these amino acids only when proline, and not ammonium, was the nitrogen source, indicating nitrogen regulation of amino acid transport.<jats:italic>ilv2<\/jats:italic>mutants rapidly lost viability at 37\u200a\u00b0C and when starved for isoleucine and valine. Consistent with these phenotypes, an<jats:italic>ilv2<\/jats:italic>mutant was avirulent and unable to survive in mice. Because<jats:italic>C. neoformans<\/jats:italic>Ilv2p is required for virulence and survival<jats:italic>in vivo<\/jats:italic>, inhibitors of branched-chain amino acid biosynthesis may make valuable antifungal agents.<\/jats:p>","DOI":"10.1099\/mic.0.26928-0","type":"journal-article","created":{"date-parts":[[2004,5,8]],"date-time":"2004-05-08T00:53:04Z","timestamp":1083977584000},"page":"1547-1558","source":"Crossref","is-referenced-by-count":71,"title":["Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37\u200a\u00b0C and in vivo"],"prefix":"10.1099","volume":"150","author":[{"given":"Joanne M.","family":"Kingsbury","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonya M.","family":"Ganous","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"McCusker","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0003-9861(77)90189-8","article-title":"Peptide transport in yeast: uptake of radioactive trimethionine in Saccharomyces cerevisiae","volume":"178","author":"Becker","year":"1977","journal-title":"Arch Biochem Biophys"},{"key":"R2","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1128\/JCM.31.10.2819-2823.1993","article-title":"Multilocus enzyme typing of Cryptococcus neoformans","volume":"31","author":"Brandt","year":"1993","journal-title":"J Clin Microbiol"},{"key":"R3","first-page":"1475","article-title":"Cryptococcus neoformans","volume":"94","author":"Bulmer","year":"1967","journal-title":"I. 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