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Here we report on the in vivo effects of cryptococcal pre-exposure to ecologically relevant nitrogen levels. <jats:italic>C. neoformans<\/jats:italic> H99 was cultured in yeast carbon base (YCB) supplemented with 0.53\u00a0g\/L NH<jats:sub>4<\/jats:sub>Cl and 0.21\u00a0g\/L NH<jats:sub>4<\/jats:sub>Cl, respectively, and used to infect larvae of the Greater Wax moth, <jats:italic>Galleria mellonella<\/jats:italic>. Cells cultured in low nitrogen YCB (LN) were more virulent compared to cells cultured in high nitrogen YCB (HN). Microscopic examination of haemolymph collected from infected larvae revealed that cells cultured in LN were larger than cells cultured in HN, with the majority of LN cells exceeding 10\u00a0\u00b5m and possibly entering titanisation. Additionally, compared to HN-cultured cells, fewer LN-cultured cells were engulfed by macrophages. The enhanced virulence of LN-cultured cells was attributed to the increased cell size in vivo. In contrast, reduced macrophage uptake was attributed to increased capsule thickness of in vitro cells. Not only do these findings demonstrate the effects of culture conditions, specifically nitrogen levels, on <jats:italic>C. neoformans<\/jats:italic> virulence, but they also highlight the importance of isolate background in the cryptococcal-host interaction.<\/jats:p>","DOI":"10.1007\/s10123-024-00504-y","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T14:03:30Z","timestamp":1710425010000},"page":"1587-1595","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exposure of Cryptococcus neoformans to low nitrogen levels enhances virulence"],"prefix":"10.1007","volume":"27","author":[{"given":"Caylin","family":"Bosch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbra","family":"Toplis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton DuPreez","family":"Van Staden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinrich","family":"Volschenk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Dicks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred","family":"Botha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"issue":"8","key":"504_CR1","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1039\/C4MT00057A","volume":"6","author":"C Angele-Martinez","year":"2014","unstructured":"Angele-Martinez C, Goodman C, Brumaghim J (2014) Metal-mediated DNA damage and cell death: mechanisms, detection methods, and cellular consequences. 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