Chemical reaction-mediated covalent localization of bacteria

Huilong Luo, Yanmei Chen, Xiao Kuang, Xinyue Wang, Fengmin Yang, Zhenping Cao, Lu Wang, Sisi Lin, Feng Wu and Jinyao Liu ()
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Huilong Luo: Shanghai Jiao Tong University
Yanmei Chen: Shanghai Jiao Tong University
Xiao Kuang: Shanghai Jiao Tong University
Xinyue Wang: Shanghai Jiao Tong University
Fengmin Yang: Shanghai Jiao Tong University
Zhenping Cao: Shanghai Jiao Tong University
Lu Wang: Shanghai Jiao Tong University
Sisi Lin: Shanghai Jiao Tong University
Feng Wu: Shanghai Jiao Tong University
Jinyao Liu: Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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 × 107 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.

Date: 2022
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DOI: 10.1038/s41467-022-35579-6

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