Selective and effective bactericidal activity of the cobalt (II) cation against Helicobacter pylori.
BACKGROUND
Although the anti-Helicobacter pylori activity of bismuth is well established, the therapeutic potential of other metal ions against the organism is not known.


METHODS
We measured the minimum inhibitory concentrations of a series of metal ions, including several cobalt (II) compounds against four type strains and seven clinical isolates of H. pylori using three standard broth culture media and a defined medium. Other intestinal bacteria were also investigated for specificity of action.


RESULTS
Cobalt chloride had marked activity against H. pylori (minimum inhibitory concentration range was 0.03-1.0 mg/l). The effect was specific because other transition metals had no effect and other intestinal bacteria were not affected by cobalt chloride. Activity was attributable to free cobalt ions as ligands inhibited activity in proportion to their affinity for the ions. Inhibition of cobalt activity was also observed in the presence of nickel, in a dose dependent fashion. However, cobalt activity was not directed towards the nickel-dependent urease enzyme because its effect was similar in wild-type and urease negative mutant strains of H. pylori. Finally, the viability of H. pylori was reduced at the same rate with 2 mg/l cobalt as with 1 mg/l amoxicillin.


CONCLUSIONS
Cobalt competes for nickel in its acquisition by H. pylori, but mediates toxicity in a nonurease dependent fashion. As cobalt MIC is similar to some antibiotics and 10 to a hundred times lower than for bismuth, cobalt may represent an effective form of therapy for H. pylori infection.
Bruggraber
Sylvaine F A
SF
Gastrointestinal Laboratory, The Rayne Institute, London, UK. sylvaine.bruggraber@mrc-hnr.cam.ac.uk
French
Gary
G
Thompson
Richard P H
RP
Powell
Jonathan J
JJ
D002413:Cations, Divalent; D003035:Cobalt / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009532:Nickel / Q000494:pharmacology
D002413:Cations, Divalent; D003035:Cobalt; D009532:Nickel; C018021:cobaltous chloride