Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties

Candida albicans is a deadly pathogen responsible for mil-lions of mucosal and systemic infections per year. The patho-biology of C. albicans is largely dependent on the damaging and immunostimulatory properties of the peptide candidalysin (CL), a key virulence factor. When CL forms pores in the plasma membrane of epithelial cells, it activates a response network grounded in activation of the epidermal growth factor receptor. Prior reviews have characterized the resulting CL immune activation schemas but lacked insights into the mo-lecular mechanism of CL membrane damage. We recently demonstrated that CL functions by undergoing a unique self-assembly process; CL forms polymers and loops in aqueous solution prior to inserting and forming pores in cell mem-branes. This mechanism, the first of its kind to be observed, informs new therapeutic avenues to treat Candida infections. Recently, variants of CL were identified in other Candida species, providing an opportunity to identify the residues that are key for CL to function. In this review, we connect the ability of CL to damage cell membranes to its immunostimulatory properties.

Automated summary

Candida albicans is a deadly pathogen that causes millions of mucosal and systemic infections per year. The peptide candidalysin plays a key role in the pathophysiology by damaging cell membranes and activating immune responses. Recent research has revealed a novel self-assembly mechanism of candidalysin, which opens up new therapeutic opportunities for treating Candida infections.