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A mucin-responsive hybrid two-component system controls Bacteroides thetaiotaomicron colonization and gut homeostasis

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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Abstract

The mammalian intestinal tract contains trillions of bacteria. However, the genetic factors that allow gut symbiotic bacteria to occupy intestinal niches remain poorly understood. Here, we identified genetic determinants required for Bacteroides thetaiotaomicron colonization in the gut using transposon sequencing analysis. Transposon insertion in BT2391, which encodes a hybrid two-component system, increased the competitive fitness of B. thetaiotaomicron. The BT2391 mutant showed a growth advantage in a mucin-dependent manner and had an increased ability to adhere to mucus-producing cell lines. The increased competitive advantage of the BT2391 mutant was dependent on the BT2392-2395 locus containing susCD homologs. Deletion of BT2391 led to changes in the expression levels of B. thetaiotaomicron genes during gut colonization. However, colonization of the BT2391 mutant promoted DSS colitis in low-fiber diet-fed mice. These results indicate that BT2391 contributes to a sustainable symbiotic relationship by maintaining a balance between mucosal colonization and gut homeostasis.

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Acknowledgements

This study was supported by the Fellowship of Suh Kyungbae Foundation to JHP, the POSCO Science Fellowship of POSCO TJ Park Foundation to JHP; and by a grant (2020R1I1A1A-01052942) of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Republic of Korea, to YJC. SJK, JYH, and SHC were recipients of the BK21 Fellowship from the Ministry of Education.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, 08826, Republic of Korea

    Ju-Hyung Lee, Soo-Jeong Kwon, Ji-Yoon Han, Sang-Hyun Cho, Yong-Joon Cho & Joo-Hong Park

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  1. Ju-Hyung Lee
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JHP initiated the project. JHL, SJK, JYH, and SHC performed the experiments. YJC helped interpret the experimental results. JHL, YJC, and JHP wrote the manuscript.

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Correspondence to Joo-Hong Park.

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Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethcial Statements All animal experiments were performed as approved by the Institutional Animal Care and Use Committee (IACUC) of Seoul National University (approval number: SNU-200504-6-6).

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Lee, JH., Kwon, SJ., Han, JY. et al. A mucin-responsive hybrid two-component system controls Bacteroides thetaiotaomicron colonization and gut homeostasis. J Microbiol. 60, 215–223 (2022). https://doi.org/10.1007/s12275-022-1649-3

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