Antimicrobial peptide LL-37 disrupts plasma membrane and calcium homeostasis in Candida albicans via the Rim101 pathway

Abstract

ABSTRACT Antimicrobial peptides play an important role in human innate defense against microbial pathogens. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides. We previously showed that LL-37 targets the cell wall of Candida albicans , thereby reducing cell adhesion to plastic surfaces, oral epidermoid cells, and urinary bladders of mice. Moreover, LL-37 also induces cell wall and endoplasmic reticulum stress responses. Here, we found that LL-37 alters plasma membrane properties. In addition, LL-37 affected calcium homeostasis and induced the generation of reactive oxygen species associated with mitochondria and vacuoles. Finally, the Rim101 pathway was linked to the cellular response to LL-37. Together, these findings provide new insights into anti- C . albicans actions of LL-37 and highlight the complex cellular responses induced by LL-37. IMPORTANCE Candida albicans is a major human fungal pathogen, and antimicrobial peptides are key components of innate immunity. Studying the interplay between C. albicans and human antimicrobial peptides would enhance a better understanding of pathogen-host interactions. Moreover, potential applications of antimicrobial peptides in antifungal therapy have aroused great interest. This work explores new mechanisms of LL-37 against C. albicans and reveals the complex connection among calcium homeostasis, oxidative stress, signaling, and possibly organelle interaction. Notably, these findings support the possible use of antimicrobial peptides to prevent and treat fungal infections.