PDF(Pubmed)
Abstract：
Salmonella enterica is a food-borne pathogen able to cause a wide spectrum of diseases ranging from mild gastroenteritis to systemic infections. During almost all stages of the infection process Salmonella is likely to be exposed to a wide variety of host-derived antimicrobial peptides (AMPs). AMPs are important components of the innate immune response which integrate within the bacterial membrane, thus forming pores which lead ultimately to bacterial killing. In contrast to other AMPs Bactericidal/Permeability-increasing Protein (BPI) displayed only weak bacteriostatic or bactericidal effects towards Salmonella enterica sv. Typhimurium (STM) cultures. Surprisingly, we found that sub-antimicrobial concentrations of BPI fold-containing (BPIF) superfamily members mediated adhesion of STM depending on pre-formed type 1 fimbriae. BPIF proteins directly bind to type 1 fimbriae through mannose-containing oligosaccharide modifications. Fimbriae decorated with BPIF proteins exhibit extended binding specificity, allowing for bacterial adhesion on a greater variety of abiotic and biotic surfaces likely promoting host colonization. Further, fimbriae significantly contributed to the resistance against BPI, probably through sequestration of the AMP before membrane interaction. In conclusion, functional subversion of innate immune proteins of the BPIF family through binding to fimbriae promotes Salmonella virulence by survival of host defense and promotion of host colonization.
摘要：
肠沙门氏菌是一种食源性病原体，能够引起广泛的疾病，从轻度胃肠炎到全身性感染。在感染过程的几乎所有阶段，沙门氏菌都可能暴露于多种宿主来源的抗微生物肽（AMP）。AMP是先天免疫反应的重要组成部分，整合在细菌膜内，从而形成孔，最终导致细菌死亡。与其他AMP相反，杀菌/通透性增加蛋白（BPI）对肠沙门氏菌仅显示出弱的抑菌或杀菌作用。鼠伤寒(STM)培养物。令人惊讶的是,我们发现，亚抗菌浓度的BPI折叠（BPIF）超家族成员介导的STM粘附取决于预先形成的1型菌毛。BPIF蛋白通过含甘露糖的寡糖修饰直接结合1型菌毛。用BPIF蛋白修饰的菌毛表现出扩展的结合特异性，允许细菌粘附在更多种类的非生物和生物表面上，可能促进宿主定植。Further,菌毛显著促进了对BPI的抗性，可能是通过在膜相互作用之前隔离AMP。总之,BPIF家族的先天免疫蛋白通过与菌毛结合的功能颠覆通过宿主防御的存活和促进宿主定植来促进沙门氏菌的毒力。
