Extensive surface diversity of a commensal microorganism by multiple DNA inversions

The dynamic interactions between a host and its intestinal microflora that lead to commensalism are unclear. Bacteria that colonize the intestinal tract do so despite the development of a specific immune response by the host. The mechanisms used by commensal organisms to circumvent this immune response have yet to be established. Here we demonstrate that the human colonic microorganism, Bacteroides fragilis, is able to modulate its surface antigenicity by producing at least eight distinct capsular polysaccharides—a number greater than any previously reported for a bacterium—and is able to regulate their expression in an on–off manner by the reversible inversion of DNA segments containing the promoters for their expression. This means of generating surface diversity allows the organism to exhibit a wide array of distinct surface polysaccharide combinations, and may have broad implications for how the predominant human colonic microorganisms, the Bacteroides species, maintain an ecological niche in the intestinal tract.

[1]  D. Kasper,et al.  Analysis of a Capsular Polysaccharide Biosynthesis Locus of Bacteroides fragilis , 1999, Infection and Immunity.

[2]  P. Klemm,et al.  Localization of promoters in the fim gene cluster and the effect of H-NS on the transcription of fimB and fimE. , 1994, FEMS microbiology letters.

[3]  D. Kasper,et al.  Bacteroides fragilis NCTC9343 Produces at Least Three Distinct Capsular Polysaccharides: Cloning, Characterization, and Reassignment of Polysaccharide B and C Biosynthesis Loci , 2000, Infection and Immunity.

[4]  M. Malamy,et al.  Sequencing the gene for an imipenem-cefoxitin-hydrolyzing enzyme (CfiA) from Bacteroides fragilis TAL2480 reveals strong similarity between CfiA and Bacillus cereus beta-lactamase II , 1990, Journal of bacteriology.

[5]  H. Mobley,et al.  In Vivo Phase Variation of Escherichia coli Type 1 Fimbrial Genes in Women with Urinary Tract Infection , 1998, Infection and Immunity.

[6]  J. Abraham,et al.  An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Kasper,et al.  Polysaccharide Biosynthesis Locus Required for Virulence of Bacteroides fragilis , 2001, Infection and Immunity.

[8]  R. Zinkernagel,et al.  A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. , 2000, Science.

[9]  Analysis of cepA and other Bacteroides fragilis genes reveals a unique promoter structure. , 2000, FEMS microbiology letters.