title: The effect of the bacterial product, succinic acid, on neutrophil bactericidal activity.
abstract: We investigated the effect of succinic acid on neutrophil bactericidal activity in a model of intra-abdominal abscess induced in mice by the peritoneal inoculation of 5 x 10(6) cfu ml-1 E. coli and 5 x 10(8) cfu ml-1 B. fragilis plus 1 mg of bran as faecal fibre analogue. The mean pH of the induced abscesses at week 1 was 6.7, higher than the pH associated with succinic acid inhibitory activity. We therefore determined the effect of succinic acid (0-100 mM) at pH 6.7 on the bactericidal activity of mouse bone marrow-derived neutrophils. Phagocytic killing of Proteus mirabilis by neutrophils was significantly inhibited by 30-100 mM succinic acid at pH 6.7 but there was no significant effect of succinic acid on engulfment of bacteria at this pH. However, significant inhibition of intracellular killing (assayed by adding succinic acid to suspensions of neutrophils which had engulfed bacteria in low serum concentrations but in the absence of succinic acid) was noted at 70 and 100 mM. These results indicate that succinic acid inhibits neutrophil bactericidal activity at a physiological pH, principally through inhibition of intracellular killing mechanisms and therefore contributing to bacterial persistence in this model of abscess formation.
authors.affiliation: Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
authors.forename: K B
authors.initials: KB
authors.lastname: Abdul-Majid
authors.forename: P A
authors.initials: PA
authors.lastname: Kenny
authors.forename: J J
authors.initials: JJ
authors.lastname: Finlay-Jones
mesh_terms: D018784:Abdominal Abscess / Q000097:blood / Q000276:immunology / Q000382:microbiology; D000818:Animals; D001442:Bacteroides Infections / Q000097:blood / Q000276:immunology; D001441:Bacteroides fragilis / Q000737:chemistry* / Q000187:drug effects; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D018845:CD11 Antigens / Q000096:biosynthesis / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry* / Q000187:drug effects; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology*; D010587:Phagocytosis / Q000187:drug effects; D011512:Proteus Infections / Q000097:blood / Q000276:immunology; D013386:Succinates / Q000494:pharmacology*; D019802:Succinic Acid
chemical_list: D018845:CD11 Antigens; D013386:Succinates; D019802:Succinic Acid