Selective inhibition of penicillin-binding proteins and its effects on growth and architecture ofStaphylococcus aureus

We found that the three high molecular weight penicillin-binding proteins (PBP) 1, 2, and 3 of Staphylococcus aureus could be blocked by the β-lactam antibiotics imipenem, cefotaxime, and mecillinam, respectively. The inhibition of any of these PBPs was not sufficient for an antibacterial effect. Even the simultaneous blocking of PBPs 2 and 3, previously supposed to be the lethal targets of β-lactam antibiotics, did not induce bacteriolysis, nor did the combined saturation of PBPs 2, 3, and 4. Instead, PBP 1 seems to play a key role, because on one hand the combined inhibition of PBP 1 with any of the other high molecular weight PBPs led to bacteriolysis, on the other hand, only inhibition of PBP 1 led to a loss of the ‘splitting system’ of the staphylococcal cross wall, similar to that observed in penicillin G-treated cells earlier.