In human hosts, the opportunistic fungal pathogen primarily proliferates in nutrient diverse niches. Environmental condition sensing regulates several fungal cellular features including, but not limited to, metabolism, cell wall elasticity, and virulence. In addition, yeast cell division exposes pathogen-associated molecular patterns (PAMPs) at the cell surface that are known to be immune-stimulatory (e.g. β-glucan). While various host environmental signals and cell wall stressors have been implicated in PAMP exposure , little is known about the molecular mechanisms that modulate PAMP exposure. We have shown that lactate, an alternative carbon source present in mucosal niches and produced by activated innate immune cells, acts as a signalling molecule to reduce β-glucan exposure. However, it is unknown whether the reduction in β-glucan exposure is the result of PAMP camouflaging by other cell wall components, PAMP modification, or a combination of both processes. We characterized the downstream effectors affecting PAMP exposure in response to different carbon sources and environmental conditions that encounters during transit through host niches. Using proteomics, gene deletion analysis, and pharmacological assays, we identified the downstream effectors involved in evading β-glucan recognition by the host pattern recognition receptor, Dectin-1. We can also show microscopic changes to the overall distribution of Dectin-1-recognised β-glucan on the cell surface in response to masking conditions as well as alterations to the interactions of masked cells with phagocytes. Finally, we are examining the impact of PAMP modulation and its inhibition on disease outcomes.


Article metrics loading...

Loading full text...

Full text loading...


Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error