Polysaccharide biosynthesis locus required for virulence of Bacteroides fragilis

Bacteroides fragilis, though only a minor component of the human intestinal commensal flora, is the anaerobe most frequently isolated from intra-abdom inal abscesses. S, fragilis 9343 expresses at least three capsular polysacc harides-polysaccharide A (PS A), PS B, and PS C, Purified PS A and PS B hav e been tested in animal models and are both able to induce the formation of intra-abdominal abscesses. Mutants unable to synthesize PS B or PS C still facilitate abscess formation at levels comparable to those of wild-type 93 43, To determine the contribution of PS A to abscess formation in the conte xt of the intact organism, the PS A biosynthesis region was cloned, sequenc ed, and deleted from 9343 to produce a PS A-negative mutant. Animal experim ents demonstrate that the abscess-inducing capability of 9343 is severely a ttenuated when the organism cannot synthesize PS A, despite continued synth esis of the other capsular polysaccharides, The PS A of 9343 contains an un usual free amino sugar that is essential for abscess formation by this poly mer. PCR analysis of the PS A biosynthesis loci of 50 B,fragilis isolates i ndicates that regions flanking each side of this locus are conserved in all strains. The downstream conserved region includes two terminal PS A biosyn thesis genes that homology-based analyses predict are involved in the synth esis and transfer of the free amino sugar of PS A. Conservation of these ge nes suggests that this sugar is present in the PS A of all serotypes and ma y explain the abscessogenic nature of B, fragilis.