Journal of Antimicrobial Chemotherapy, Vol 41, 171-177, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
P Kaihovaara, J Hook-Nikanne, M Uusi-Oukari, TU Kosunen and M Salaspuro
Helicobacter pylori flavodoxin was purified to homogeneity from cell
extracts of strain NCTC 11637. The molecular weight of the protein was
estimated by gel electrophoresis to be 18 kDa. Oxidized flavodoxin showed
an absorption spectrum with maxima at 378 nm and 453 nm, and it was reduced
to a neutral form of flavin semiquinone by the electrons generated in the
oxidation of pyruvate. This coenzyme A dependent pyruvate:flavodoxin
oxidoreductase activity of H. pylori was also detected as a reduction of
methyl viologen or cytochrome c by bacterial extracts. The apparent Km of
pyruvate was 310 microM. Anaerobically incubated bacteria (10[9]) of strain
NCTC 11637 produced acetate (96 +/- 16 nmol/h) from pyruvate concomitantly
reducing metronidazole (17 +/- 5 nmol/h). In anaerobic conditions both
sensitive and resistant H. pylori strains reduced metronidazole, and there
was a significant positive correlation between acetate production and
metronidazole activation (r = 0.77, P < 0.01, n = 11). In the presence
of atmospheric oxygen, H. pylori excreted twice as much acetate but
metronidazole was not activated. These results suggest that the
pyruvate:flavodoxin oxidoreductase complex catalyses pyruvate oxidation in
H. pylori. Electrons generated in this reaction are transferred to
flavodoxin and under anaerobic conditions further to metronidazole
(imidazoles) thus reducing the drug to its bactericidal form.
ORIGINAL ARTICLES
Flavodoxin-dependent pyruvate oxidation, acetate production and metronidazole reduction by Helicobacter pylori
Research Unit of Alcohol Diseases, Institute of Biomedicine, University of Helsinki, Finland.
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