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The differences in the outer membrane permeation between two major subgroups of beta-lactam antibiotics were studied. The permeation of cephalosporins was closely related to porin channels in the outer membrane. In contrast, the outer membrane permeation of penicillins did not decrease in porin-deficient mutants and, in Rd-type mutants, their permeability became proportional to the hydrophobicity of the molecules. The activation enthalpy of the penicillin permeation was significantly larger than that of cephalosporins. These observations indicate that penicillins can use the hydrophobic region for the major route of outer membrane passage whereas the cephalosporin permeation is restricted to the pathway via the porin pore.
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