We have examined the effects of acidic pH, in the range of those prevailing within phagosomes and lysosomes, on the growth and the susceptibility to different antibiotics of several strains of spp. The minimal inhibitory concentration and the minimal bactericidal concentration of several β-lactams were increased considerably during culture at pH 5·2. The extent of the increase was a function of: (1) the β-lactam structure and, more particularly, the hydrophobicity of the side-chain of the molecule;and (2) the bacterial serotype. This phenotypic resistance at acid pH was not due to β-lactamase activity or to a lower growth rate. In contrast, rifamycin SV was more active at acidic pH than at neutral pH and chloramphenicol, another highly hydrophobic drug, was equally efficacious at both pH values. Membrane lipopolysac-charide mutants, but not porin mutants, cultivated at an acidic pH were inhibited by lower concentrations of the β-lactams. This suggests that the increased resistance to β-lactams, and the increased susceptibility to rifamycin SV, at acidic pH, could have resulted from modified permeability of the outer membrane to antibiotics.


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