The Mechanism of the Bacteriostatic Action of Tetrachlorosalicylanilide: a Membrane-active Antibacterial Compound

Abstract

SUMMARY The antibacterial action of the skin germicides tetrachlorosalicylanilide, tribromosalicylanilide, trichlorocarbanilide and monochlorophenoxysali-cylanilide against Staphylococcus aureus, depends on the reversible adsorption of the germicides on the cell membrane. Bacteriostasis results from the adsorption of, respectively, 0·75 × 105, 2·0 × 105, 5·1 × 105 and 7·2 × 105 molecules of germicide per bacterium. The resistance of Escherichia coli to these compounds results from a decreased adsorption, which is a property of the cell wall. It is proposed that the membrane-active antibacterial compounds, detergents, phenols, quaternary ammonium compounds, poly-peptide antibiotics and the germicides under study in this paper, share a common mechanism of action, in which the adsorption of the compound on the cell membrane is a critical step. Resistance to these compounds results from the inhibition of the penetration through the cell wall to the combining sites on the membrane. At the cellular bacteriostatic concentration, the effect of tetrachlorosalicylanilide on the biochemical activities of Staphylococcus aureus has been studied. The energy-dependent transport of phosphate and amino acids into the bacteria is inhibited, whereas the energy-independent entry of phosphate, amino acids and glucose is unaffected. The energy-dependent incorporation of lysine and glucose into cellular material is also inhibited. The release of amino acids from the cell pool into the medium results from the inhibition of the energy-dependent processes involved in the maintenance of the amino acid pool. This inhibition of energy metabolism by the germicide at its bacteriostatic concentration is sufficient to cause the inhibition of growth.