Abstract
Phase changes in Bacteroides fragilis, a member of the human colonic microbiota, mediate variations in a vast array of cell surface molecules, such as capsular polysaccharides and outer membrane proteins through DNA inversion. The results of the present study show that outer membrane vesicle (OMV) formation in this anaerobe is also controlled by DNA inversions at two distantly localized promoters, IVp-I and IVp-II that are associated with extracellular polysaccharide biosynthesis and the expression of outer membrane proteins. These promoter inversions are mediated by a single tyrosine recombinase encoded by BF2766 (orthologous to tsr19 in strain NCTC9343) in B. fragilis YCH46, which is located near IVp-I. A series of BF2766 mutants were constructed in which the two promoters were locked in different configurations (IVp-I/IVp-II = ON/ON, OFF/OFF, ON/OFF or OFF/ON). ON/ON B. fragilis mutants exhibited hypervesiculating, whereas the other mutants formed only a trace amount of OMVs. The hypervesiculating ON/ON mutants showed higher resistance to treatment with bile, LL-37, and human β-defensin 2. Incubation of wild-type cells with 5% bile increased the population of cells with the ON/ON genotype. These results indicate that B. fragilis regulates the formation of OMVs through DNA inversions at two distantly related promoter regions in response to membrane stress, although the mechanism underlying the interplay between the two regions controlled by the invertible promoters remains unknown.
Highlights
The gut is the part of the human body that is most densely populated with diverse microorganisms
The results of the present study included the novel observation that promoter inversion is a mechanism for outer membrane vesicle (OMV) formation in B. fragilis
Because enhanced OMV production was observed only in the ON/ON genotype with respect to IVp-I/IVp-II, and because IVp-II-regulated gene expression was increased in this mutant, an elevated outer membrane protein level driven by this gene cluster was considered necessary for hypervesiculation
Summary
The gut is the part of the human body that is most densely populated with diverse microorganisms. The microbial composition markedly differs throughout the intestinal tract [1], indicating that the human gut harbors unique microbe-microbe and host-microbe interactions that depend on the location in the digestive tract. Intestinal microbes must adapt to the environmental changes in their habitats including changes in nutrient availability and the levels of antimicrobial substances produced by host immunity. Because microbial adaptations reflect the characteristics of their habitats, identifying the adaptation mechanisms of gut microbes will increase the current understanding of the intestinal environment. Because the cell surface is the first point of contact with host components, cell surface adaptation is important for gut bacteria to sense and survive various environmental stimuli [2]
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