In vitro and in vivo characterisation of isolates of cryptococcus 1 neoformans causing meningitis in hiv infected and uninfected patients

27 Most cryptococcal meningitis cases occur in immunocompromised individuals and are caused 28 by Cryptococcus neoformans var.grubii. We previously reported cryptococcal meningitis in 29 Vietnam arising atypically in HIV-uninfected, apparently immunocompetent patients, caused by 30 a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans (VNI-γ). This 31 variant was less common in HIV-infected individuals. It is unclear why this lineage is associated 32 with HIV-uninfected, apparently immunocompetent patients. To better delineate the 33 phenotypic characteristics of C. neoformans VNI-γ in comparison with other C. neoformans 34 lineages we selected 30 representative isolates and compared their genotype-specific in vitro 35 pathogenic potential and in vivo virulence, and ability to induce inflammatory response in the 36 A/J mouse model. All isolates were genotyped using multi-locus sequence typing. All previously 37 AFLP-defined VNI-γ isolates were identified as sequence type (ST) 5. Compared with non-ST5 38 strains, ST5 isolates had significantly increased variability in cell and capsule size (p<0.001). ST5 39 and non-ST5 strains exhibited similar characteristics in relation to previously defined virulence 40 factors including melanization, growth at 37C, and growth in cerebrospinal fluid. However, A/J 41 . CC-BY-NC-ND 4.0 International license under a not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available The copyright holder for this preprint (which was this version posted September 15, 2017. ; https://doi.org/10.1101/189274 doi: bioRxiv preprint