Cryptococcus neoformans responds to presence of mycobacterium by diversifying its morphologies and remodelling its capsular material

Cryptococcus neoformans and Mycobacterium tuberculosis are opportunistic pathogens that share overlapping geographical distributions and physiological niches within the human body. Both are recognised by the World Health Organization as high-priority pathogens. Although clinical reports of co-infections with cryptococcosis and tuberculosis are increasing, experimental studies exploring their interactions remain scarce. Here, we demonstrate that C. neoformans can grow in physiologically relevant human plasma-like medium in the presence of either heat-killed M. tuberculosis antigen or the live vaccine strain, M. bovis BCG. In response to presence of mycobacteria, C. neoformans increased in number and exhibited enhanced virulence-associated traits, including titan cell formation, capsule enlargement and increased survival from phagocytosis. This work provides proof-of-principle for a dynamic, inter-pathogen interaction that may contribute to exacerbation disease outcomes in settings of a co-infection.