Journal Article

Secretory IgA reduced the ergosterol contents of Candida albicans to repress its hyphal growth and virulence

Chen, Xi, Chen, Ding, Gou, Lichen, Ren, Biao, Liu, Yaqi, Cheng, Lei, Zhou, Xuedong, Wang, Jiannan, Shen, Jiawei, Shi, Yangyang, Zong, Yawen, Liao, Binyou, Wei, Yu

2024

Overview

Ca ndid a albicans , one of the most prevalent conditional pathogenic fungi, can cause local superficial infections and lethal systemic infections, especially in the immunocompromised population. Secretory immunoglobulin A (sIgA) is an important immune protein regulating the pathogenicity of C. albicans . However, the actions and mechanisms that sIgA exerts directly against C. albicans are still unclear. Here, we investigated that sIgA directs against C. albicans hyphal growth and virulence to oral epithelial cells. Our results indicated that sIgA significantly inhibited C. albicans hyphal growth, adhesion, and damage to oral epithelial cells compared with IgG. According to the transcriptome and RT-PCR analysis, sIgA significantly affected the ergosterol biosynthesis pathway. Furthermore, sIgA significantly reduced the ergosterol levels, while the addition of exogenous ergosterol restored C. albicans hyphal growth and adhesion to oral epithelial cells, indicating that sIgA suppressed the growth of hyphae and the pathogenicity of C. albicans by reducing its ergosterol levels. By employing the key genes mutants ( erg11Δ/Δ , erg3Δ/Δ , and erg3Δ/Δ erg11Δ/Δ ) from the ergosterol pathway, sIgA lost the hyphal inhibition on these mutants, while sIgA also reduced the inhibitory effects of erg11Δ/Δ and erg3Δ/Δ and lost the inhibition of erg3Δ/Δ erg11Δ/Δ on the adhesion to oral epithelial cells, further proving the hyphal repression of sIgA through the ergosterol pathway. We demonstrated for the first time that sIgA inhibited C. albicans hyphal development and virulence by affecting ergosterol biosynthesis and suggest that ergosterol is a crucial regulator of C. albicans -host cell interactions. Key points • sIgA repressed C. albicans hyphal growth • sIgA inhibited C. albicans virulence to host cells • sIgA affected C. albicans hyphae and virulence by reducing its ergosterol levels

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Adhesion / Applied Microbial and Cell Physiology / Biomedical and Life Sciences / Biosynthesis / Biotechnology / Candida albicans / Candida albicans - genetics / Cell interactions / Epithelial Cells / Epithelium / Ergosterol / Hyphae / immunocompromised population / Immunoglobulin A / Immunoglobulin A, Secretory / Immunoglobulin G / Life Sciences / Microbial Genetics and Genomics / Microbiological research / Microbiology / Mutants / Pathogenicity / Pathogens / Physiological aspects / reverse transcriptase polymerase chain reaction / transcriptome / Transcriptomes / Virulence / Virulence (Microbiology)