Chairatana Phoom, Chiang I-Ling, Nolan Elizabeth M
Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Biochemistry. 2017 Feb 28;56(8):1033-1041. doi: 10.1021/acs.biochem.6b01111. Epub 2017 Jan 23.
Human α-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.
人α-防御素6（HD6）是一种宿主防御肽，通过形成捕获细菌并防止细菌侵袭上皮细胞的非共价寡聚体，有助于肠道固有免疫并介导黏膜表面的稳态。这项研究揭示了HD6在保护宿主上皮细胞免受病原微生物侵害方面的新作用。我们报告称，HD6可阻止白色念珠菌黏附于人类肠道上皮细胞，并抑制白色念珠菌的两种毒力特性，即侵袭人类上皮细胞和生物膜形成。此外，对HD6与不形成高阶寡聚体的单点变体F2A的比较表明，HD6的自组装特性对于其抗白色念珠菌的功能活性至关重要。这种机会性真菌病原体在健康个体的肠道中作为肠道微生物群的一员存在，可转变为致病状态并导致从浅表感染到危及生命的全身感染等多种疾病。我们的结果表明，HD6可能使白色念珠菌在胃肠道中作为无害的共生菌持续存在。此外，HD6及受其启发的分子可能为探索新的抗菌策略提供基础，这些策略可减弱白色念珠菌和其他微生物病原体的毒力特性。
