Dissemination ofCryptococcus neoformansvia localised proliferation and blockage of blood vessels

Abstract

26Cryptococcus neoformans is an opportunistic fungal pathogen that can cause life-27 threatening cryptoccocal meningitis, predominantly within immunocompromised individuals. 28Cortical infarcts are observed in as many as 30% of cryptococcal meningitis cases, being 29 particularly common in severe infection. Limited clinical case studies suggest infarcts are 30 secondary to vasculitis and blood vessel damage caused by cryptococcal infection. 31However, the cause of infarcts in cryptococcal infection has not been determined. To 49Although vasculature inflammation in known to occur in cryptococcal meningitis, the cause 50 of infarcts in unknown. Using a zebrafish model of cryptococcal infection, the growth and 51. CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/184200 doi: bioRxiv preprint first posted online 3 dissemination of fungal cells was observed over time. We show that cryptococcal cells 52 become trapped and proliferate in the vasculature, resulting in cryptococcoma that damage 53 the blood vessels. We propose that vessel damage results from increased blood pressure 54 caused by cryptococci blocking blood vessels suggesting that the vascular damage that 55 ensues on cryptococcoma formation may in turn be a cause of infarct formation seen in 56 cryptococcal meningitis.