Human α-Defensin 6 Self-Assembly Prevents Adhesion and Suppresses Virulence Traits of Candida albicans
Human α-Defensin 6 Self-Assembly Prevents Adhesion and Suppresses Virulence Traits of Candida albicans
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DOI：
10.1021/acs.biochem.6b01111
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发表时间：
2017-02-28
期刊：
影响因子：
2.9
通讯作者：
Nolan, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Chairatana, Phoom;Chiang, I-Ling;Nolan, Elizabeth M.
人α-防御素6（HD 6）是一种宿主防御肽，其有助于肠道先天免疫并通过形成捕获细菌并防止细菌侵入上皮的非共价寡聚体来介导粘膜表面的稳态。这项工作说明了HD 6在保护宿主上皮免受病原微生物侵害方面的新作用。我们报道HD 6阻断白色念珠菌对人肠上皮细胞的粘附，并抑制两种念珠菌。白色念珠菌毒力特征，即侵入人体上皮细胞和生物膜形成。此外，HD 6和不形成高阶寡聚体的单点变体F2 A的比较表明，HD 6的自组装特性对于抗C.白色念珠菌这种机会性真菌病原体作为健康个体肠道微生物群的一员存在于肠道中，可以变成有毒的，并引起各种疾病，从浅表感染到危及生命的全身性感染。我们的结果表明，HD 6可能允许C.白色念珠菌在胃肠道中作为无害的寄生虫持续存在。此外，HD 6和HD 6启发的分子可能为探索新的抗微生物策略提供基础，以减弱C.白色念珠菌和其它微生物病原体。
Human alpha-defensin 6 (HD6) is a host-defense peptide that contributes to intestinal innate immunity and mediates homeostasis at mucosal surfaces by forming noncovalent oligomers that capture bacteria and prevent bacterial invasion of the epithelium. This work illustrates a new role of HD6 in defending the host epithelium against pathogenic microorganisms. We report that HD6 blocks adhesion of Candida albicans to human intestinal epithelial cells and suppresses two C. albicans virulence traits, namely, invasion of human epithelial cells and biofilm formation. Moreover, a comparison of HD6 and a single-point variant F2A that does not form higher-order oligomers demonstrates that the self-assembly properties of HD6 are essential for functional activity against C. albicans. This opportunistic fungal pathogen, which resides in the intestine as a member of the gut microbiota in healthy individuals, can turn virulent and cause a variety of diseases ranging from superficial infections to life-threatening systemic infections. Our results indicate that HD6 may allow C. albicans to persist as a harmless commensal in the gastrointestinal tract. Moreover, HD6 and HD6-inspired molecules may provide a foundation for exploring new antimicrobial strategies that attenuate the virulence traits of C. albicans and other microbial pathogens.