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Updated: Aug 17, 2025

Engineering Adherent Bacteria by Creating a Single Synthetic Curli Operon
Published on: November 16, 2012
Chemical reaction-mediated covalent localization of bacteria
Huilong Luo1, Yanmei Chen1, Xiao Kuang1
1Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
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.
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