Succinic Acid Production by Bacteroides fragilis: A Potential Bacterial Virulence Factor

We previously demonstrated that Bacteroides species elaborate a factor that impairs polymorphonuclear leukocyte (PMN) migration. This factor, active at a pH of 5.5 but not at 7.4, had similar inhibitory characteristics as the Bacteroides metabolite succinic acid. We examined the kinetics of production of this inhibitory factor and correlated its presence with succinic acid concentrations in the culture filtrate. In the four to six hours after Bacteroides fragilis 9032 reached the stationary phase of growth, there was a large increase in succinic acid production with an accompanying reduction in culture pH. This correlated well with the generation of a leukocyte-inhibitory factor. Pure succinic acid in sterile culture medium at concentrations similar to those detected in the 18-hour culture filtrate (20 mmol/L) produced comparable reduction in PMN migration. Following gel filtration chromatography of B fragilis culture filtrate, the fractions containing succinic acid labeled with carbon 14 inhibited PMN migration.