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Incubation of pneumococci with d-alanine-containing peptides naturally occurrins in peptidoglycan protected cells against lysis and killing by β-lactam antibiotics near MIC. Such peptides caused decreased binding of the antibiotic to penicillin-binding proteins (PBPs), primarily PBP 2B. This provides direct evidence in vivo for the hypothesis that β-lactams act as substrate analogues and identifies PBP 2B as a killing target in pneumococci.
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