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We investigated specific interactions between <jats:italic>Cn<\/jats:italic>-<jats:italic>Hc<\/jats:italic> to determine the impact of synchronous infection in virulence and disease. Co-infected mice had significantly higher mortality than infection with either species or acapsular <jats:italic>Cn<\/jats:italic>-<jats:italic>Hc<\/jats:italic>. Coating of <jats:italic>Hc<\/jats:italic> with cryptococcal glycans (<jats:italic>Cn<\/jats:italic>-gly) resulted in higher pulmonary fungal burden in co-infected animals relative to control. Co-cultivation or addition of <jats:italic>Cn<\/jats:italic>-gly resulted in enhanced pellicle formation with a hybrid polysaccharide matrix with higher reactivity to GXM mAbs. Transfer and incorporation of <jats:italic>Cn<\/jats:italic> polysaccharide onto <jats:italic>Hc<\/jats:italic> surface was time and temperature dependent. <jats:italic>Cn-<\/jats:italic>gly transfer altered the zeta potential of <jats:italic>Hc<\/jats:italic> and was associated with increased resistance to phagocytosis and killing by macrophages. Mice infected with <jats:italic>Hc<\/jats:italic> and subsequently injected with purified <jats:italic>Cn<\/jats:italic>-gly died significantly more rapidly than <jats:italic>Hc<\/jats:italic> alone infected, establishing the precedent that virulence factors from one fungus can enhance the virulence of unrelated species. These findings suggest a new mechanism of microbial interaction involving the transfer of virulence traits that translates into enhanced lethality during mixed fungal infections and highlights the importance of studying heterogeneous microbial populations in the setting of infection.<\/jats:p>","DOI":"10.1038\/srep21765","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T10:37:23Z","timestamp":1456310243000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection"],"prefix":"10.1038","volume":"6","author":[{"given":"Radames J. 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