Effect of luxS encoding a synthase of quorum-sensing signal molecule AI-2 of Vibrio vulnificus on mouse gut microbiome

Abstract

Autoinducer-2 (AI-2), a quorum-sensing signal molecule from the human pathogen Vibrio vulnificus, was assessed for its effect on the gut microbiome of mice. For this, we employed 16S rRNA sequencing to compare the gut microbiome of mice infected with either wild-type V. vulnificus or with the isotype ΔluxS that has a deletion in luxS which encodes the biosynthetic function of AI-2. The relative ratio of wild-type Vibrio species in the jejunum and ileum of mice infected with the wild type was significantly higher than that in mice infected with ΔluxS, suggesting that AI-2 plays an important role in the colonization of V. vulnificus in the small intestine. The bacterial composition in the gut of mice infected with ΔluxS comprises a higher proportion of Firmicutes, composed mainly of Lactobacillus, compared to the mice infected with wild-type cells. In the large intestine, Vibrio species were barely detected regardless of genetic background. Three Lactobacillus spp. isolated from fecal samples from mice infected with ΔluxS manifested significant antibacterial activities against V. vulnificus. Culture supernatants from these three species were dissolved by HPLC, and a substance in fractions showing inhibitory activity against V. vulnificus was determined to be lactic acid. Our results suggest that luxS in V. vulnificus affects not only the ability of the species to colonize the host gut but also its susceptibility to the growth-inhibiting activity of commensal bacteria including Lactobacillus. KEY POINTS: • Gut microbiomes of ΔluxS-infected and WT Vibrio-infected mice differed greatly. • Difference was most prominent in the jejunum and ileum compared to the duodenum or large intestine. • In the small and large intestines of mice, the relative proportions of Vibrio and Lactobacillus species showed a negative relationship. • Effector molecules produced by Lactobacillus in mouse gut inhibit Vibrio growth.

Keywords: AI-2; Lactic acid; Lactobacillus; Microbiome; Quorum-sensing; Vibrio vulnificus.