Mode of Synergism between Colistin and Sulfisomezole in Inhibiting the Growth of Proteus Organism

Abstract

When either colistin at 1,000 μg/ml or sulfisomezole at 125 μg/ml was used separately, growth of a strain of Proteus mirabilis was not inhibited. However, when 1 μg/ml of colistin and 25 μg/ml of sulfisomezole were used together in agar media, growth was inhibited. The synergistic action of colistin and sulfisomezole was also demonstrated in broth culture, when a smaller inoculum such as 106 cells/ml was used. The lethal and lytic effect of this synergism parallels the characteristic effect of colistin towards colistin-sensitive gram-negative organisms. When the mode of this synergistic action was analyzed by adding each compound in sequence to a growing culture of Proteus, it was found that growth of organism for about 4 generations in the presence of sulfisomezole was a prerequisite for revealing the lethal and lytic effects of colistin. In cultures where these two compounds were present at the beginning of incubation, the synergistic effect was abolished by the addition of p-aminobenzoic acid (PABA) at an early stage of incubation, but not at a late stage. Methionine, serine, and betaine, when used together, had the same effect as PABA. An insufficiency of the three compounds induced by sulfisomezole, was considered to afford the receptor site of colistin to Proteus.