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We used killing of the nematode <jats:italic>Caenorhabditis elegans<\/jats:italic> by <jats:italic>C. neoformans<\/jats:italic> as an assay to screen a library of random <jats:italic>C. neoformans<\/jats:italic> insertion mutants. Of 350 mutants tested, seven were identified with attenuated virulence that persisted after crossing the mutation back into a wild\u2010type strain<jats:italic>.<\/jats:italic> Genetic analysis of one strain revealed an insertion in a gene homologous to <jats:italic>Saccharomyces cerevisiae KIN1<\/jats:italic>, which encodes a serine\/threonine protein kinase. <jats:italic>C. neoformans kin1<\/jats:italic> mutants exhibited significant defects in virulence in murine inhalation and haematogenous infection models and displayed increased binding <jats:bold>to alveolar and peritoneal macrophages<\/jats:bold>. The <jats:italic>kin1<\/jats:italic> mutant phenotypes were complemented by the wild\u2010type <jats:italic>KIN1<\/jats:italic> gene. These findings show that the <jats:italic>C. neoformans<\/jats:italic> Kin1 kinase homologue is required for full virulence in disparate hosts and that <jats:italic>C. elegans<\/jats:italic> can be used as a substitute host to identify novel factors involved in fungal pathogenesis in mammals.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2004.04310.x","type":"journal-article","created":{"date-parts":[[2004,10,6]],"date-time":"2004-10-06T15:50:24Z","timestamp":1097077824000},"page":"407-419","source":"Crossref","is-referenced-by-count":65,"title":["<i>Cryptococcus neoformans<\/i> Kin1 protein kinase homologue, identified through a <i>Caenorhabditis elegans<\/i> screen, promotes virulence in 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