A Bacteroides By-product Inhibits Human Polymorphonuclear Leukocyte Function

We have previously demonstrated that Bacteroides fragilis enhanced Escherichia coli–induced lethality in the rat fibrin—clot peritonitis model. As a possible mechanism for this phenomenon, it was hypothesized that B fragilis inhibited host defense mechanisms, allowing the E coli to flourish and kill the animal. Culture filtrates of three Bacteroides species were tested in vitro for their effect on human polymorphonuclear leukocyte (PMN) chemotaxis and random migration. Two of these, B fragilis and Bacteroides distasonis, impaired PMN migration. The other, Bacteroides thetaiotaomicron, caused variable inhibition of neutrophil chemotaxis. The ability of the culture filtrates to inhibit neutrophil function appeared to depend on two factors: (1) adequate growth of the Bacteroides culture, permitting production of the leukotoxic factor, and (2) reduction of the culture pH to a level at which the putative toxin could exert its effect. Further studies revealed that the factor was heat stable, had a molecular weight less than 500, and that its effect on PMNs was only partially reversed by multiple washings. This supports the concept that Bacteroides species may contribute to the pathogenicity of mixed infections by producing a factor that inhibits host neutrophil function.