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Extensive surface diversity of a commensal microorganism by multiple DNA inversions

Abstract

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 host1. 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.

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Figure 1: Western immunoblot analysis of reactivity of monospecific antisera with wild type and mutants.
Figure 2: Phase-variable expression of capsular polysaccharides of B. fragilis.
Figure 3: DNA inversions between inverted repeats account for phase-variable promoter activity.
Figure 4: Polysaccharide expression correlates with the orientation of the invertible promoter regions.

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Acknowledgements

We thank W. Kalka-Moll for electron microscope photography and J. Daley and S. Lazo-Kallanian for assistance with FACS analysis. This work was supported by grants from the National Institutes of Health.

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Correspondence to Laurie E. Comstock.

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Krinos, C., Coyne, M., Weinacht, K. et al. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature 414, 555–558 (2001). https://doi.org/10.1038/35107092

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