共生菌之间的共生关系由月光蛋白的共享来介导。

Sharing of Moonlighting Proteins Mediates the Symbiotic Relationship among Intestinal Commensals.

机构信息

Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, Japan.

出版信息

Appl Environ Microbiol. 2023 Mar 29;89(3):e0219022. doi: 10.1128/aem.02190-22. Epub 2023 Feb 27.

Abstract

The human gastrointestinal tract is inhabited by trillions of symbiotic bacteria that form a complex ecological community and influence human physiology. Symbiotic nutrient sharing and nutrient competition are the most studied relationships in gut commensals, whereas the interactions underlying homeostasis and community maintenance are not fully understood. Here, we provide insights into a new symbiotic relationship wherein the sharing of secreted cytoplasmic proteins, called "moonlighting proteins," between two heterologous bacterial strains (Bifidobacterium longum and Bacteroides thetaiotaomicron) was observed to affect the adhesion of bacteria to mucins. B. longum and B. thetaiotaomicron were cocultured using a membrane-filter system, and in this system the cocultured B. thetaiotaomicron cells showed greater adhesion to mucins compared to that shown by monoculture cells. Proteomic analysis showed the presence of 13 B. longum-derived cytoplasmic proteins on the surface of B. thetaiotaomicron. Moreover, incubation of B. thetaiotaomicron with the recombinant proteins GroEL and elongation factor Tu (EF-Tu)-two well-known mucin-adhesive moonlighting proteins of B. longum-led to an increase in the adhesion of B. thetaiotaomicron to mucins, a result attributed to the localization of these proteins on the B. thetaiotaomicron cell surface. Furthermore, the recombinant EF-Tu and GroEL proteins were observed to bind to the cell surface of several other bacterial species; however, the binding was species dependent. The present findings indicate a symbiotic relationship mediated by the sharing of moonlighting proteins among specific strains of B. longum and B. thetaiotaomicron. The adhesion of intestinal bacteria to the mucus layer is an important colonization strategy in the gut environment. Generally, the bacterial adhesion process is a characteristic feature of the individual cell surface-associated adhesion factors secreted by a particular bacterium. In this study, coculture experiments between and show that the secreted moonlighting proteins adhere to the cell surface of coexisting bacteria and alter the adhesiveness of the bacteria to mucins. This finding indicates that the moonlighting proteins act as adhesion factors for not only homologous strains but also for coexisting heterologous strains. The presence of a coexisting bacterium in the environment can significantly alter the mucin-adhesive properties of another bacterium. The findings from this study contribute to a better understanding of the colonization properties of gut bacteria through the discovery of a new symbiotic relationship between them.

摘要

人体胃肠道中栖息着数以万亿计的共生细菌,这些细菌形成了一个复杂的生态群落,并影响着人类的生理机能。共生的营养物质共享和营养物质竞争是研究肠道共生菌最广泛的关系,而维持体内平衡和群落维持的相互作用还没有完全理解。在这里,我们提供了一个新的共生关系的见解,其中两种异源细菌(长双歧杆菌和拟杆菌)之间共享分泌的细胞质蛋白,称为“月光蛋白”,被观察到影响细菌对粘蛋白的黏附。长双歧杆菌和拟杆菌在膜过滤系统中进行共培养,在这个系统中,共培养的拟杆菌细胞对粘蛋白的黏附性比单培养细胞更强。蛋白质组学分析显示,在拟杆菌表面存在 13 种长双歧杆菌衍生的细胞质蛋白。此外,将重组蛋白 GroEL 和延伸因子 Tu(EF-Tu)-长双歧杆菌中两种众所周知的粘蛋白结合月光蛋白孵育拟杆菌,导致拟杆菌对粘蛋白的黏附增加,这归因于这些蛋白在拟杆菌细胞表面的定位。此外,观察到重组 EF-Tu 和 GroEL 蛋白与其他几种细菌的细胞表面结合;然而,这种结合是物种依赖性的。本研究结果表明,长双歧杆菌和拟杆菌特定菌株之间通过共享月光蛋白而介导的共生关系。肠道细菌对黏液层的黏附是在肠道环境中重要的定植策略。一般来说,细菌的黏附过程是特定细菌分泌的个体细胞表面相关黏附因子的特征。在这项研究中,和的共培养实验表明,分泌的月光蛋白黏附在共存细菌的细胞表面,并改变细菌对粘蛋白的黏附性。这一发现表明,月光蛋白不仅作为同源菌株的黏附因子,而且作为共存的异源菌株的黏附因子。环境中共存细菌的存在可以显著改变另一种细菌对粘蛋白的黏附特性。这项研究的发现有助于通过发现它们之间的新共生关系,更好地理解肠道细菌的定植特性。

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