Cryptococcus gattii responds to mycobacterial exposure through coordinated remodelling of population dynamics and cell surface architecture, enhancing pulmonary persistence in a co-infection model

Irere, H.; San, Z. N.; Mukaremera, L.; Dambuza, I. M.

doi:10.64898/2026.05.25.727575

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bioRxiv · 10.64898/2026.05.25.727575

Cryptococcus gattii responds to mycobacterial exposure through coordinated remodelling of population dynamics and cell surface architecture, enhancing pulmonary persistence in a co-infection model

Irere, H.·San, Z. N.·Mukaremera, L.·Dambuza, I. M.

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Abstract

Cryptococcus neoformans and Cryptococcus gattii are major causes of fungal pneumonia and meningitis, frequently co-occurring with Mycobacterium tuberculosis in endemic regions, where co-infection is associated with increased mortality. Yet, how Cryptococcus adapts to mycobacterial co-presence within the lung remains poorly understood. Here, we show that mycobacterial cues trigger a conserved adaptive programme in C. gattii, mirroring responses previously observed in C. neoformans. Increasing exposure to mycobacteria drives cell and capsule enlargement and promotes titan cell formation, accompanied by dose-dependent remodelling of chitin and chitosan. Importantly, in vivo exposure to heat-killed mycobacteria increases C. gattii pulmonary burden, linking structural remodelling to enhanced persistence. These findings identify mycobacterial co-presence as a driver of fungal phenotypic plasticity and reveal pathogen-pathogen interactions as critical regulators of disease outcome, highlighting a previously unrecognised axis of co-infection relevant to C. gattii pathogenesis and therapeutic strategy.

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Irere, H., San, Z. N., Mukaremera, L., Dambuza, I. M.. 2026-05-25. Cryptococcus gattii responds to mycobacterial exposure through coordinated remodelling of population dynamics and cell surface architecture, enhancing pulmonary persistence in a co-infection model. https://doi.org/10.64898/2026.05.25.727575

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