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

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Abstract
The antibacterial action of the skin germicides tetrachlorosallcylanllide, tribromo-salicylanilide, trichlorocarbanilide and monochlorophenoxysalicylanilide against Staphylococcus aureus, depends on the reversible adsorption of the germicides on the cell membrane. Bacteriostasis results from the adsorption of, respectively. 0.75 x 10-5, 2.0 x 105, 5.1 x 105 and 7.2 x 105 molecules of germicide per bacterium. The resistance of Escherichia coli to these compounds results from a decreased adsorp-tion, which is a property of the cell wall. The membrane-active antibacterial compounds, detergents, phenols, quaternary ammonium compounds, polypeptide antibiotics and the germicides studied may 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 S. aureus was 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 processes involved in the maintenance of the amino add pool. This inhibition of energy metabolism by the germicide at its bacteriostatic concentration is sufficient to cause the inhibition of growth.