Identification of the target site of antimicrobial peptide AMP-17 against <i>Candida albicans</i>.

Longbing Yang; Zhuqing Tian; Luoxiong Zhou; Chaoqin Sun; Mingjiao Huang; Chunren Tian; Jian Peng; Guo Guo

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Identification of the target site of antimicrobial peptide AMP-17 against Candida albicans.

Author: Longbing YANG ¹ ; Zhuqing TIAN ¹ ; Luoxiong ZHOU ¹ ; Chaoqin SUN ¹ ; Mingjiao HUANG ¹ ; Chunren TIAN ¹ ; Jian PENG ¹ ; Guo GUO ¹
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1. The Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, Guizhou, China.
Publication Type:Journal Article
Keywords: AMP-17; Candida albicans; SRR1; XOG1; antimicrobial peptide; clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9)
MeSH: Humans; Candida albicans; Antimicrobial Peptides; Proteomics; Peptides/pharmacology*; Transcription Factors/metabolism*; Antifungal Agents/pharmacology*
From: Chinese Journal of Biotechnology 2023;39(1):304-317
CountryChina
Language:Chinese
Abstract: Candida albicans is one of the major causes of invasive fungal infections and a serious opportunistic pathogen in immunocompromised individuals. The antimicrobial peptide AMP-17 has prominent anti-Candida activity, and proteomic analysis revealed significant differences in the expression of cell wall (XOG1) and oxidative stress (SRR1) genes upon the action of AMP-17 on C. albicans, suggesting that AMP-17 may exert anti-C. albicans effects by affecting the expression of XOG1 and SRR1 genes. To further investigate whether XOG1 and SRR1 genes were the targets of AMP-17, C. albicans xog1Δ/Δ and srr1Δ/Δ mutants were constructed using the clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system. Phenotypic observations revealed that deletion of two genes had no significant effect on C. albicans growth and biofilm formation, whereas XOG1 gene deletion affected in vitro stress response and mycelium formation of C. albicans. Drug sensitivity assay showed that the MIC₈₀ values of AMP-17 against xog1Δ/Δ and srr1Δ/Δ mutants increased from 8 μg/mL (for the wild type C. albicans SC5314) to 16 μg/mL, while the MIC₈₀ values against srr1Δ/Δ: : srr1 revertants decreased to the level of the wild type SC5314. In addition, the ability of AMP-17 to inhibit biofilm formation of both deletion strains was significantly reduced compared to that of wild type SC5314, indicating that the susceptibility of the deletion mutants to AMP-17 was reduced in both the yeast state and during biofilm formation. These results suggest that XOG1 and SRR1 genes are likely two of the potential targets for AMP-17 to exert anti-C. albicans effects, which may facilitate further exploration of the antibacterial mechanism of novel peptide antifungal drugs.