One of the most important fungal pathogens is Cryptococcus neoformans, which, when inhaled, grows in the lung, escapes our immune defenses, and translocates to the brain, causing meningitis. One way that Cryptococcus escapes immune cells is by extreme changes in cell size.
So-called titan cells are much larger than immune cells, and can both evade host immunity and protect smaller cells. They are also associated with drug resistance, making them important to treatment targets. But how these cells form is largely unknown.
We have shown that exposure to physiologically relevant conditions and bacterial cell wall triggers a morphological switch from haploid yeast to polyploid titan cells. Building on our in vitro model of the yeast-to-titan switch, we seek to understand the molecular mechanisms that enable this transition.
This work is funded by grants from the BBSRC, the Wellcome Trust, and the NC3Rs.