title: DNA Inversion Regulates Outer Membrane Vesicle Production in Bacteroides fragilis.
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.
authors: Department of Microbiology, Faculty of Medicine, Kagawa University, 1750-1 Miki, Kagawa 761-0793, Japan.
authors: Haruyuki
authors: H
authors: Nakayama-Imaohji
authors: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
authors: Katsuhiko
authors: K
authors: Hirota
authors: Department of Cellular and Molecular Medicine, Wakayama Medical University Graduate School of Medicine, Wakayama 641-8509, Japan.
authors: Hisashi
authors: H
authors: Yamasaki
authors: Department of Microbiology, Faculty of Medicine, Kagawa University, 1750-1 Miki, Kagawa 761-0793, Japan.
authors: Saori
authors: S
authors: Yoneda
authors: Department of Microbiology, Faculty of Medicine, Kagawa University, 1750-1 Miki, Kagawa 761-0793, Japan.
authors: Hirofumi
authors: H
authors: Nariya
authors: Department of Microbiology, Faculty of Medicine, Kagawa University, 1750-1 Miki, Kagawa 761-0793, Japan.
authors: Motoo
authors: M
authors: Suzuki
authors: Inserm UMR1043 Toulouse, France.|INRA USC 1360 Toulouse, France.|CNRS UMR5282 Toulouse, France.|Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.
authors: Thomas
authors: T
authors: Secher
authors: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
authors: Yoichiro
authors: Y
authors: Miyake
authors: Inserm UMR1043 Toulouse, France.|INRA USC 1360 Toulouse, France.|CNRS UMR5282 Toulouse, France.|Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.|CHU Toulouse, Hôpital Purpan, Service de bactériologie-hygiène, Toulouse, France.
authors: Eric
authors: E
authors: Oswald
authors: Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Tetsuya
authors: T
authors: Hayashi
authors: Department of Microbiology, Faculty of Medicine, Kagawa University, 1750-1 Miki, Kagawa 761-0793, Japan.
authors: Tomomi
authors: T
authors: Kuwahara
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis*; D001441:Bacteroides fragilis / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D000067128:Extracellular Vesicles / Q000378:metabolism / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D040901:Proteomics; D057345:Sequence Inversion / Q000235:genetics* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins