Abstract
BackgroundThe C10 family of cysteine proteases includes enzymes that contribute to the virulence of bacterial pathogens, such as SpeB in Streptococcus pyogenes. The presence of homologues of cysteine protease genes in human commensal organisms has not been examined. Bacteroides fragilis is a member of the dominant Bacteroidetes phylum of the human intestinal microbiota, and is a significant opportunistic pathogen.ResultsFour homologues of the streptococcal virulence factor SpeB were identified in the B. fragilis genome. These four protease genes, two were directly contiguous to open reading frames predicted to encode staphostatin-like inhibitors, with which the protease genes were co-transcribed. Two of these protease genes are unique to B. fragilis 638R and are associated with two large genomic insertions. Gene annotation indicated that one of these insertions was a conjugative Tn-like element and the other was a prophage-like element, which was shown to be capable of excision. Homologues of the B. fragilis C10 protease genes were present in a panel of clinical isolates, and in DNA extracted from normal human faecal microbiota.ConclusionsThis study suggests a mechanism for the evolution and dissemination of an important class of protease in major members of the normal human microbiota.
Highlights
The C10 family of cysteine proteases includes enzymes that contribute to the virulence of bacterial pathogens, such as Streptococcal pyrogenic exotoxin B (SpeB) in Streptococcus pyogenes
The B. fragilis genome harbours four paralogous C10 protease genes A phylogenetic study was undertaken to determine the relatedness of C10 proteases in other members of the Bacteroidetes phylum (Fig. 1)
This study has established the presence of homologues of the streptococcal virulence factor SpeB in a significant gut microorganism, B. fragilis
Summary
The C10 family of cysteine proteases includes enzymes that contribute to the virulence of bacterial pathogens, such as SpeB in Streptococcus pyogenes. Bacteroides fragilis is a member of the dominant Bacteroidetes phylum of the human intestinal microbiota, and is a significant opportunistic pathogen. Bacteroides fragilis is a Gram-negative member of the normal human gut microbiota. B. fragilis is an important opportunistic pathogen, and it is the most frequently isolated anaerobic bacterium in clinical specimens, including abdominal abscesses and bloodstream infections [2]. While B. fragilis accounts for only 4 to 13% of the normal human fecal microbiota, it is responsible for 63 to 80% of Bacteroides infections [3]. A few virulence factors have been described for B. fragilis, with the best characterized being the polysaccharide (PS) capsule [4] and a secreted metalloprotease, fragilysin [5].
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