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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