Some Aspects of the Mode of Action of the Antibacterial Compound Bronopol (2‐bromo‐2‐nitropropan‐1,3‐diol)

Abstract

A series of nitro compounds studied inhibited Eecherichia coli, ~taphylococcua aureue and P 8 e U d O V l O W aeruginosa, bronopol being the mout active derivative. Bronopol causes some membrane damage. A consideration of its action on enzyme activity, reaction with cell constituents and chemical reaction with cysteine, glutathiono and proteins suggests that the oxidation of thiol groups t o disulphides may be its primary action. ZSOLNAI (1961) examined a number of alkyl and aralkyl nitro compounds and demonstrat,eci the antifungal activity of this group, particularly where the structural feature, CBrNO,, was present. Eckstcin et al. (1963) described the antifungal activity of some 2-nitropropan-l,3-01 derivatives and showed that 2-bromo-2-nitropropan-1,3 tliol was one of the more active compounds. Croshaw, Groves & Lessel (1964) studied the activity of 2-bromo-2-nitropropan-l,3-diol (bronopol) and found it to be active against both Gram positive and Gram negative bacteria, being particularly active against Pseudomonas aeruginosa, and exhibiting activity against yeasts and fungi. The bacteriostatic action was decreased in the presence of cysteine hydrochloride, serum or horse blood. The wide spectrum of activity makes it suitable for use as a preservative in pliarmaceutical products (Sykes, 1969), and because of its lack of irritancy combined with stability in aqueous solution, Bryce & Smart (1965) recommended its use in shampoo formulations. Brown (1966) showed that bronopol was rapidly active against Ps. aeruginosa and unaffected by the presence of nonionic detergents. Materials and Methods OrganismsEscherichia coli NCTC 9001 , Staphylococcus aureus NCIB 8626 and Pseudomom aeruginosa NCIB 8295 were used throughout, and Bacillus megaterium NCIB 9521 for the preparation of protoplasts. MediaThe organisms were maintained in a nutrient broth containing (g/l): Oxoid beef extract, 10; Oxoid neutralized peptone, 10; sodium chloride, 6. Solid media were * Present address, Rexford Ltd, Manningtree, Essex. 1611 62 R. J. Stretton and T. W. Manson prepared by adding 1.5% w/v of Oxoid agar No. 3. A drug neutralizing medium was prepared by adding 0-1 1 yo of sodium thioglycollate. The pH value of all media was adjusted to 7.2. Chemicals Bronopol (2-bromo-2-nitropropan-l,3-diol) is a white, odourless, crystalline solid, map. 121 O, and is readily soluble in water. The sample used was a gift from The Boots Co. Ltd, Nottingham, England. The other diol nitro compounds examined, 2-nitro propan-1,3-diol and 2-chloro-2-nitropropan-l,3-diol were prepared by the method of Eckstein et al. (1963). 2-Dinitropropane, 2,3-nitro-2-methylbutane, 2-bromo-2nitropropane, 2-chloro-2-nitropropane and 2-bromo-2-nitro-3,3-dimethylbutane were prepared by Dr W. R. Bowman of this Department. Sterile solutions of the nitro compounds were prepared by filtration through a membrane filter of 0.2 pm porosity (Sartorius Membrane filter, V.

The intrinsic resistance of Escherichia coli to various antimicrobial agents requires ppGpp and sigmas

“…In CF1652, the MIC values for the β‐lactam antibiotics (Penicillin G to Cephalothin) which inhibit cell wall synthesis, were twofold less than those observed for the parent CF1648. A similar pattern of results were observed for trimethoprim, which blocks tetrahydrofolate synthesis, and is widely used against E. coli infections; polymyxin, which disrupts the structure and permeability of the plasma membrane; gentamicin which inhibits protein synthesis; 1,2‐benzisothiazolin‐3‐one (BIT) and Bronopol which chemically react with ‐SH‐containing protein/enzyme cellular components and are particularly active against actively metabolizing cells ( Crowshaw, Groves & Lessel 1964; Stretton & Mason 1973).…”

Antibacterial action of 2-bromo-2-nitropropane-1,3-diol (bronopol)

“…The results of previous TLC studies suggest that in the presence of air the major reaction product of cysteine and bronopol is cystine (16). This result was readily confirmed with equimolar amounts of the two reactants by using a combination of 1H NMR and TLC, with the additional observation that consumption of cysteine was not accompanied by any measurable loss of bronopol.…”

“…Previous studies of the mechanism of action of bronopol all conclude that the antibacterial activity of bronopol relates to its interaction with essential thiols within the cell (3,16,18). Such interaction is thought to lead to the oxidation of thiols through a radical anion intermediate (11).…”

Methods to eradicate soft tunic syndrome (STS)-causing protozoa Azumiobodo hoyamushi, the highly infectious parasite from the edible ascidian (Halocynthia roretzi)

“…While bronopol causes membrane damage in organisms through the inhibition of membrane bound enzymes (Stretton and Manson 1973). On the other hand, H 2 O 2 releases reactive oxygen species to denature proteins and lipids in the organisms (Maris 1995).…”