Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation

doi:10.1073/pnas.0404172101

Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation

^*Department of Molecular Bacteriology, Graduate School of Medicine, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; ^‡Kitasato Institute for Life Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan; ^§Graduate School of Systems Life Sciences and ^∥Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan; ^¶Center for Basic Research, Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; ^**Human Genome Research Group, RIKEN Genome Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; and ^††Department of Microbiology, Miyazaki Medical College, and Division of Bioenvironmental Science, Frontier Science Research Center, University of Miyazaki, 5200 Kiyotake, Miyazaki 899-1692, Japan

Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved September 2, 2004 (received for review June 11, 2004)

Abstract

Bacteroides are predominant human colonic commensals, but the principal pathogenic species, Bacteroides fragilis (BF), lives closely associated with the mucosal surface, whereas a second major species, Bacteroides thetaiotaomicron (BT), concentrates within the colon. We find corresponding differences in their genomes, based on determination of the genome sequence of BF and comparative analysis with BT. Both species have acquired two mechanisms that contribute to their dominance among the colonic microbiota: an exceptional capability to use a wide range of dietary polysaccharides by gene amplification and the capacity to create variable surface antigenicities by multiple DNA inversion systems. However, the gene amplification for polysaccharide assimilation is more developed in BT, in keeping with its internal localization. In contrast, external antigenic structures can be changed more systematically in BF. Thereby, at the mucosal surface, where microbes encounter continuous attack by host defenses, BF evasion of the immune system is favored, and its colonization and infectious potential are increased.

Footnotes

↵ † To whom correspondence may be addressed. E-mail: tomomi{at}basic.med.tokushima-u.ac.jp or ohnishi{at}basic.med.tokushima-u.ac.jp.
Author contributions: T.K. designed research; T.K., A.Y., H.H., H.N., H.T., N.O., S.K., M.H., T.H., and Y.O. performed research; T.K., A.Y., H.H., H.N., H.T., N.O., S.K., M.H., T.H., and Y.O. analyzed data; and T.K. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: BF, Bacteroides fragilis; BT, B. thetaiotaomicron; PG, Porphyromonas gingivalis; IR, inverted repeat sequence; CTn, conjugative transposon; PS loci, polysaccharide biosynthesis loci.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AP006841 and AP006842).