Cryptococcus neoformans α Strains Preferentially Disseminate to the Central Nervous System during Coinfection

Abstract

ABSTRACT Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species ( gattii , grubii , and neoformans ). Each variety manifests differences in epidemiology and disease, and var. grubii strains are responsible for the vast majority of human disease. In previous studies, α strains were more virulent than congenic a strains in var. neoformans , whereas var. grubii congenic a and α strains exhibited equivalent levels of virulence. Here the role of mating type in the virulence of var. grubii was further characterized in a panel of model systems. Congenic var. grubii a and α strains had equivalent survival rates when cultured with amoebae, nematodes, and macrophages. No difference in virulence was observed between a and α congenic strains in multiple inbred-mouse genetic backgrounds, and there was no difference in accumulations in the central nervous system (CNS) late in infection. In contrast, during coinfections, a and α strains are equivalent in peripheral tissues but α cells have an enhanced predilection to penetrate the CNS. These studies reveal the first virulence difference between congenic a and α strains in the most common pathogenic variety and suggest an explanation for the prevalence of α strains in clinical isolates.