{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:40:26Z","timestamp":1790232026558,"version":"4.1.0"},"reference-count":55,"publisher":"Microbiology Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,9,1]]},"abstract":"This paper describes (i) the expression profile of the methionine synthase gene (MET6<\/jats:italic>) in the human pathogenic fungus Cryptococcus neoformans<\/jats:italic> and (ii) the phenotypes of a C. neoformans met6<\/jats:italic> mutant. In contrast to the MET3<\/jats:italic> gene, which showed no significant change in expression in any environmental condition tested, the MET6<\/jats:italic> gene showed a substantial induction in response to methionine and a dramatic transcriptional induction in response to homocysteine. Like a met3<\/jats:italic> mutant, the met6<\/jats:italic> mutant was a methionine auxotroph. However, relative to a met3<\/jats:italic> mutant, the met6<\/jats:italic> mutant grew very slowly and was less heat-shock resistant. In contrast to a met3<\/jats:italic> mutant, the met6<\/jats:italic> mutant lost viability when starved of methionine, and it was deficient in capsule formation. Like a met3<\/jats:italic> mutant, the met6<\/jats:italic> mutant was avirulent. In contrast to a met3<\/jats:italic> mutant, the met6<\/jats:italic> mutant was hypersensitive to fluconazole and to the calcineurin inhibitors FK506 and cyclosporin A. A synergistic fungicidal effect was also found between each of these drugs and met6<\/jats:italic>. The phenotypic differences between the met3<\/jats:italic> and met6<\/jats:italic> mutants may be due to the accumulation in met6<\/jats:italic> mutants of homocysteine, a toxic metabolic intermediate that inhibits sterol biosynthesis.<\/jats:p>","DOI":"10.1099\/mic.0.27235-0","type":"journal-article","created":{"date-parts":[[2004,9,6]],"date-time":"2004-09-06T23:52:38Z","timestamp":1094514758000},"page":"3013-3023","source":"Crossref","is-referenced-by-count":71,"title":["Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence"],"prefix":"10.1099","volume":"150","author":[{"given":"Renata C.","family":"Pascon","sequence":"first","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":"Joanne M.","family":"Kingsbury","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, Infectious Disease Division, 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":"3206","DOI":"10.1101\/gad.11.23.3206","article-title":"Cryptococcus neoformans mating and virulence are regulated by the G-protein \u03b1 subunit GPA1 and cAMP","volume":"11","author":"Alspaugh","year":"1997","journal-title":"Genes Dev"},{"key":"R2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1128\/EC.1.1.75-84.2002","article-title":"Adenylyl cyclase functions downstream of the G\u03b1 protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans","volume":"1","author":"Alspaugh","year":"2002","journal-title":"Eukaryot Cell"},{"key":"R3","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1096\/fasebj.4.5.2407589","article-title":"Cobalamin-dependent methionine synthase","volume":"4","author":"Banerjee","year":"1990","journal-title":"FASEB J"},{"key":"R4","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0925-4439(02)00085-6","article-title":"From natural products to clinically useful antifungals","volume":"1587","author":"Barrett","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"R5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/BF00436235","article-title":"Aspects of physiology of Histoplasma capsulatum","volume":"67","author":"Boguslawski","year":"1979","journal-title":"Mycopathologia"},{"key":"R6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/yea.798","article-title":"Sulphur amino acid synthesis in Schizosaccharomyces pombe represents a specific variant of sulphur metabolism in fungi","volume":"19","author":"Brzywczy","year":"2002","journal-title":"Yeast"},{"key":"R7","first-page":"1475","article-title":"Cryptococcus neoformans","volume":"94","author":"Bulmer","year":"1967","journal-title":"I. 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