Molecular Docking Reveals Critical Residues in Candida albicans Cyr1 for Peptidoglycan Recognition and Hyphal Growth

• DOI: 10.1021/acsinfecdis.3c00115
• Publication Date: 2023-06-15T14:56:31Z
• Authors: Allan Wee Ren Ng; Lanxin Li; Evan Wei Long Ng; Chenyu Li; Yuan Qiao
• Keywords: Fungal protein; Docking (animal)

The key virulent characteristic of Candida albicans, the major fungal pathogen in humans, lies its ability to switch between benign yeast state and invasive hyphal form upon exposure specific stimuli. Among numerous hyphal-inducing signals, bacterial peptidoglycan fragments (PGNs) represent most potent inducers C. albicans growth. sole adenylyl cyclase Cyr1 is a known sensor for PGNs activates downstream signaling growth, yet molecular details PGN-Cyr1 interactions have remained unclear. In this study, we performed silico docking PGN motif modeled structure leucine-rich repeat (LRR) domain uncovered four putative PGN-interacting residues Cyr1_LRR. critical roles these binding supporting growth were demonstrated by in-gel fluorescence assay induction assay, respectively. Remarkably, mutant harboring cyr1 variant allele that defective recognition exhibits significantly reduced cytotoxicity macrophage infection assay. Overall, our work offered important insights into protein, establishing disruption results virulence albicans. Our findings provide an exciting starting point future development antagonists as novel anti-virulence therapeutics combat infection.