1 in vitro and in vivo characterisation of isolates of cryptococcus 1 neoformans causing meningitis in hiv infected and uninfected patients 2 in vietnam 3 4

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 peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/189274 doi: bioRxiv preprint first posted online Sep. 15, 2017;