Altered penicillin-binding components in penicillin-resistant mutants of Bacillus subtilis.

Abstract

Penicillin- (cloxacillin-) resistant mutants of B. subtilis were isolated in a stepwise fashion and the 5 penicillin-binding components (PBCs) in each were examined to determine which of the proteins, if any, corresponds to the penicillin killing site. PBCs III and V were previously eliminated as the likely penicillin target. In the present work, PBC IV showed no change in sensitivity to cloxacillin in any of the resistant mutants isolated. PBC I did not change until the 5th-step mutant, in which it could not be detected by penicillin binding. Since PBC I did not bind penicillins that are lethal for this mutant, it also cannot be the lethal target. PBC II showed increased resistance to cloxacillin in 3 discrete steps, i.e., in mutants 1, 4 and 5, accompanied by changes in its electrophoretic mobility. The sensitivity of PBC II to penicillin G changed very little. Correspondingly, the cloxacillin-resistant mutants were unaltered in their sensitivity to penicillin G in vivo. Of the 5 PBCs found in B. subtilis, PBC II is the most likely target for killing by penicillins.