Shigella flexneri inhibition by acetic acid

The degree of Shigella flexneri inhibition by acetic acid in a chemically defined medium was dependent upon the concentration of undissociated acetic acid in the medium. Under the conditions of the experiments, the critical concentration of undissociated acetic acid that completely inhibited S. flexneri multiplication was approximately 0.0018 M. Adjustment of the medium from pH 6.0 to 7.0 after incubation, which reduced the concentration of undissociated acid 10-fold, completely reversed inhibition, and S. flexneri attained a viable population equivalent to its population in medium without acetic acid. The effects of acetic acid on cellular processes were also studied. The acid interfered with the intracellular accumulation of glucose and glutamic acid but did not interfere with the accumulation of phosphate. The glucose analogue 3-o-methyl-D-glucose, which is taken up by S. flexneri but not metabolized, was used to determine if inhibition resulted from interference with permeation or interference with intracellular accumulation through inhibition of glucose metabolism. Acetic acid did not interfere with the uptake of the glucose analogue by S. flexneri, indicating that inhibition probably involves interference with metabolism. Further evidence for this conclusion was obtained from respiration studies with cell-free extracts in the presence and absence of acetic acid. Inhibition of oxygen uptake by acetic acid in the absence of a permeability barrier suggested a metabolic block rather than interference with permeation. The inhibition of oxygen uptake by cell-free extracts occurred at both pH 6.0 and 7.0, indicating that the degree of dissociation of the acid is unimportant regarding interference with metabolism by intracellular material. The degree of dissociation is important, however, regarding uptake of acetic acid by S. flexneri. Whole cells were more permeable to the undissociated form of acetic acid than to the dissociated form. The data indicate that acetic acid, when taken up by S. flexneri, interferes with the metabolism of glucose by the cells.