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

J Microbiol. 2022 Feb;60(2):215-223. doi: 10.1007/s12275-022-1649-3. Epub 2022 Feb 1.

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.

Keywords: Bacteroides thetaiotaomicron; colitis; colonization; hybrid two-component system; mucin.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Bacteroides thetaiotaomicron / genetics*
  • Bacteroides thetaiotaomicron / metabolism*
  • Colitis / chemically induced
  • DNA Transposable Elements
  • Gain of Function Mutation
  • Gastrointestinal Microbiome*
  • Gene Expression Regulation, Bacterial
  • Genetic Fitness
  • Germ-Free Life
  • HT29 Cells
  • Homeostasis
  • Host Microbial Interactions
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mucins / metabolism*
  • Mutagenesis
  • Mutagenesis, Insertional
  • RNA, Bacterial
  • Symbiosis

Substances

  • Bacterial Proteins
  • DNA Transposable Elements
  • Mucins
  • RNA, Bacterial