Antibacterial action of 2-bromo-2-nitropropane-1,3-diol (bronopol).
Patterns of growth inhibition of Escherichia coli in the presence of 2-bromo-2-nitropropane-1,3-diol (bronopol) indicate a period of biocide-induced bacteriostasis followed by growth at an inhibited rate. The length of the bacteriostatic period, but not the subsequent growth inhibition, was reduced by the addition of excess cysteine. Patterns of growth inhibition were unaffected by catalase or superoxide dismutase. The bactericidal concentrations (100 to 500 micrograms/ml) were considerably in excess of the MIC (13 micrograms/ml) and generally produced first-order reductions in viability. Bactericidal activity was considerably reduced by anoxic conditions and by the presence of catalase or superoxide dismutase. Results indicate that there are two distinct reactions between bronopol and thiols. Under aerobic conditions, bronopol catalytically oxidizes thiol-containing materials such as cysteine, with atmospheric oxygen as the final oxidant. By-products of this reaction are active oxygen species such as superoxide and peroxide, which are directly responsible for the bactericidal activity of the compound and for the reduced growth rate after the bacteriostatic period. The latter effect probably results from the oxidation of intracellular thiols such as glutathione and cysteine. Catalytic oxidation of thiols in the presence of excess thiol leads to the creation of an anoxic state. Under these conditions, the slower reaction with thiols, which consumes bronopol, predominates. Consumption of bronopol by its reaction with thiols, without the involvement of oxygen, leads to the eventual removal of bronopol from treated suspensions and the resumption of growth.
Shepherd
J A
JA
Department of Pharmacy, University of Manchester, United Kingdom.
Waigh
R D
RD
Gilbert
P
P
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D008956:Models, Chemical; D010101:Oxygen Consumption / Q000187:drug effects; D011409:Propylene Glycols / Q000378:metabolism / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D005609:Free Radicals; D011409:Propylene Glycols; D013438:Sulfhydryl Compounds; C006827:bronopol; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D003545:Cysteine