Abstract：
Veillonella parvula, prototypical member of the oral and gut microbiota, is at times commensal yet also potentially pathogenic. The definition of the molecular basis tailoring this contrasting behavior is key for broadening our understanding of the microbiota-driven pathogenic and/or tolerogenic mechanisms that take place within our body. In this study, we focused on the chemistry of the main constituent of the outer membrane of V. parvula, the lipopolysaccharide (LPS). LPS molecules indeed elicit pro-inflammatory and immunomodulatory responses depending on their chemical structures. Herein we report the structural elucidation of the LPS from two strains of V. parvula and show important and unprecedented differences in both the lipid and carbohydrate moieties, including the identification of a novel galactofuranose and mannitol-containing O-antigen repeating unit for one of the two strains. Furthermore, by harnessing computational studies, in vitro human cell models, as well as lectin binding solid-phase assays, we discovered that the two chemically diverse LPS immunologically behave differently and have attempted to identify the molecular determinant(s) governing this phenomenon. Whereas pro-inflammatory potential has been evidenced for the lipid A moiety, by contrast a plausible \"immune modulating\" action has been proposed for the peculiar O-antigen portion.
摘要：
细小静脉菌,口腔和肠道微生物群的典型成员，有时是共生的，但也有潜在的致病性。定制这种对比行为的分子基础的定义是扩大我们对发生在我们体内的微生物群驱动的致病和/或耐受性机制的理解的关键。在这项研究中,我们关注的是细小弧菌外膜主要成分的化学，脂多糖(LPS)。LPS分子确实根据其化学结构引起促炎和免疫调节应答。在这里，我们报告了来自两株细小弧菌的LPS的结构阐明，并显示了脂质和碳水化合物部分的重要和前所未有的差异，包括鉴定两种菌株之一的新型呋喃半乳糖和含甘露醇的O-抗原重复单元。此外，通过利用计算研究，体外人类细胞模型，以及凝集素结合固相测定，我们发现两种化学上不同的LPS在免疫学上表现不同，并试图鉴定控制这种现象的分子决定因素。是否已证明脂质A部分具有促炎潜力，相比之下，对于特殊的O抗原部分，已经提出了一种合理的“免疫调节”作用。
