Expression of pathogen‐like Opa adhesins in commensal Neisseria: genetic and functional analysis
Expression of pathogen‐like Opa adhesins in commensal Neisseria: genetic and functional analysis
复制标题
共生奈瑟菌中病原体样 Opa 粘附素的表达：遗传和功能分析
作者：
M. Toleman;E. Aho;M. Virji
几种共生奈瑟菌 (Cn) 可能定植于人类鼻咽部，但对其粘附机制知之甚少。我们研究了 Cn 和脑膜炎奈瑟菌 (Nm) 粘附素之间的结构和功能相似性，Nm 也是鼻咽部的常见定植菌。在这项研究中，我们证明了九种 Cn 菌株中 Opa 样蛋白的表达。系统发育分析将大部分 Cn Opa 分离到与致病簇分开的簇中，但有一些例外。位于致病簇内的一个 Opa 与淋病奈瑟氏球菌 (Ng) 菌株的 Opa 惊人相似 (74%)，并且与 Ng 一样，它缺乏额外的 Y11 或 136DKF138 三联体插入片段，而这些插入片段在许多脑膜炎奈瑟氏球菌 Opa 蛋白中是保守的。最重要的是，大多数 Cn Opa 蛋白能够与人类 CEACAM1 (CD66a) 分子相互作用，这些分子先前被确定为致病性 Opa 蛋白的受体。通过使用 CEACAM1 N 结构域突变体，我们证明 Cn Opa 靶向与 Nm 所使用的受体 N 结构域相同的区域。此外，Cn 菌株与细胞表达的人 CEACAM1 结合。在竞争测定中，对 CEACAM1 表现出高亲和力的贴壁 Cn 菌株 C450 不会被 Nm 分离株取代，反之亦然。但在同时培养过程中，Nm 战胜了 Cn 菌株。这是第一项证明 Cn 中粘附素表达的研究，其在结构和功能上与致病性粘附素密切相关。研究表明，一些 Cn 有可能占据人类粘膜上的受体，从而与病原体竞争，这是它们共同且专有的生态位。
Several species of commensal Neisseriae (Cn) may colonize the human nasopharynx, but little is known about their adhesion mechanisms. We have investigated structural and functional similarities between adhesins of Cn and of Neisseria meningitidis (Nm), also a frequent colonizer of the nasopharynx. In this study, we demonstrate the expression of Opa‐like proteins in nine strains of Cn. Phylogenetic analysis segregated the majority of the Cn Opa in a cluster separated from the pathogenic cluster with a few exceptions. One Opa, which located within the pathogenic cluster, was strikingly similar (74%) to an Opa of a Neisseria gonorrhoeae (Ng) strain and, like Ng, it lacked the extra Y11 or the 136DKF138 triplet insert, which are conserved among many N. meningitidis Opa proteins. Most importantly, the majority of the Cn Opa proteins were able to interact with human CEACAM1 (CD66a) molecules, previously identified as receptors for pathogenic Opa proteins. By the use of CEACAM1 N‐domain mutants, we demonstrate that Cn Opa target the same region of the N‐domain of the receptor as that used by Nm. Furthermore, Cn strains bound to cell‐expressed human CEACAM1. In competition assays, adherent Cn strain C450, exhibiting high affinity for CEACAM1, was not displaced by a Nm isolate and vice versa. But in simultaneous incubation, Nm out‐competed the Cn strain. This is the first study to demonstrate the expression of adhesins in Cn that are structurally and functionally closely related to pathogenic adhesins. The studies imply that some Cn have the potential to occupy and thus compete with the pathogens for receptors on human mucosa, their common and exclusive niche.
影响因子：
11.4
作者：
VANNHIEU, GT;ISBERG, RR
通讯作者：
ISBERG, RR