Chemical reaction-mediated covalent localization of bacteria

• Published in: Nature communications Vol. 13; no. 1; pp. 7808 - 13
• Main Authors: Luo, Huilong, Chen, Yanmei, Kuang, Xiao, Wang, Xinyue, Yang, Fengmin, Cao, Zhenping, Wang, Lu, Lin, Sisi, Wu, Feng, Liu, Jinyao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/28; 14/34; 631/92/2783; 639/166/985; 639/638/542/967; Amino groups; Bacteria; Catalysts; Chemical reactions; Covalence; Disulfides - chemistry; Humanities and Social Sciences; Intestinal microflora; Jejunum; Localization; Microbiota; Mucin; Mucins; Mucositis; multidisciplinary; Probiotics; Remission; Science; Science (multidisciplinary); Small intestine; Sulfhydryl Compounds - chemistry; Thiols; Transplantation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35579-6

Methods capable of manipulating bacterial colonization are of great significance for modulating host-microbiota relationships. Here, we describe a strategy of in-situ chemical reaction-mediated covalent localization of bacteria. Through a simple one-step imidoester reaction, primary amino groups on bacterial surface can be converted to free thiols under cytocompatible conditions. Surface thiolation is applicable to modify diverse strains and the number of introduced thiols per bacterium can be easily tuned by varying feed ratios. These chemically reactive bacteria are able to spontaneously bond with mucous layer by catalyst-free thiol-disulfide exchange between mucin-associated disulfides and newly converted thiols on bacterial surface and show thiolation level-dependent attachment. Bacteria optimized with 9.3 × 10 7 thiols per cell achieve 170-fold higher attachment in mucin-enriched jejunum, a challenging location for gut microbiota to colonize. As a proof-of-concept application for microbiota transplantation, covalent bonding-assisted localization of an oral probiotic in the jejunum generates an improved remission of jejunal mucositis. Our findings demonstrate that transforming bacteria with a reactive surface provides an approach to chemically control bacterial localization, which is highly desirable for developing next-generation bacterial living bioagents. Transplantation of helpful bacteria has been used to treat disease through modulating host microbiota. Here, the authors report a strategy to control bacteria localization in the jejunum, via an in vivo in-situ thiol-disulfide exchange reaction between surface-reactive bacteria and mucous.