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 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.

Reconstructing immune phylogeny: new perspectives

“…In various pathogens, including bacteria and protozoan parasites, several fundamental mechanisms of DNA change are used during invasion of the host. DNA recombination [148][149][150][151] , gene conversion [152][153][154] and gene hypermutation can lead to the evasion of host detection and to the subsequent clonal selection of the pathogenic variant. For example, in trypanosomes, DNA recombination and gene conversion rapidly modify variant surface glycoproteins and allow evasion of host detection 155,156 .…”

The redox potential interferes with the expression of laminin binding molecules in Bacteroides fragilis

“…Recent analyses of the genome sequences revealed DNA inversion regions. These results suggested that the ability of B. fragilis to colonise several host environments, behaving either as a member of the microbiota or a pathogen, might be linked to switching of polysaccharide biosynthesis (Krinos et al 2001).…”

“…The capsular polysaccharide complex (CPC) is a crucial factor in the virulence potential of the species (Comstock et al 1999, Coyne et al 2000. B. fragilis modulates its surface antigenicity, generating distinct CPC combinations (Krinos et al 2001). High variation in the polysaccharide expression of B. fragilis has already been demonstrated using monoclonal antibodies (Patrick et al 1999).…”

“…Recent analyses of the genome sequences revealed DNA inversion regions. These results suggested that the ability of B. fragilis to colonise several host environments, behaving either as a member of the microbiota or a pathogen, might be linked to switching of polysaccharide biosynthesis (Krinos et al 2001).The extracellular matrix (ECM) is a stable macromolecular structure underlying epithelial and endothelial cells and surrounding connective tissue cells. In the ECM, collagens, proteoglycans and structural glycoproteins, such as fibronectin and laminin, are found and these molecules are usually exploited for colonisation by microbes (Ljungh et al 1996).…”

“…This complex has a zwitterion nature (Stingele et al 2004) and a critical involvement in abscess formation (Coyne et al 2000). B. fragilis can modulate its surface antigenicity (phase dependent) and it has at least eight distinct polysaccharides (PSA to PSH) (Krinos et al 2001). It is well documented that the CPC is involved in abscess formation (Stingele et al 2004).…”