Penicillin-binding protein in Acinetobacter baumannii (PBP)

Penicillin-binding proteins in Acinetobacter baumannii are a family of enzymes critical for bacterial cell-wall peptidoglycan synthesis, especially for transpeptidation and sometimes transglycosylation. They are essential for maintenance of cell shape and proliferation, and are the direct targets of β-lactam antibiotics. Modification of PBPs, either by mutation or altered expression, is a key mechanism underlying β-lactam resistance in A. baumannii, a pathogen notorious for multidrug resistance. Multiple PBPs exist, with PBP2 playing a prominent role in cell shape and PBP1a, PBP3, etc. contributing to peptidoglycan assembly. Recent structural biology studies reveal metal (zinc) binding sites in PBP2 required for function, implicating metal-chelation as a possible therapeutic strategy. PBPs remain crucial targets for the development of new antimicrobials aimed at combating infections caused by drug-resistant A. baumannii. Key PBPs in Acinetobacter baumannii: - PBP1a: class A, with both glycosyltransferase and transpeptidase activity - PBP2: class B, major role in cell shape and wall elongation - PBP3: class B, involved in cell division - Other PBPs: variable expression and molecular weights (see clinical studies for specifics) Role in resistance: Alterations in PBPs—reduced affinity for β-lactams, expression changes, acquisition of low-affinity forms—underpin many β-lactam resistance phenotypes. PBPs can also work in concert with efflux pumps or β-lactamase enzymes for multifactorial resistance. Summary: Penicillin-binding proteins in Acinetobacter baumannii are archetypal targets for β-lactam antibiotics, act as central determinants of cell wall biosynthesis, and contribute to the pathogen's formidable resistance mechanisms.

Other names

penicillin-binding proteinPBPclass A PBP (PBP1a)class B PBP (PBP2, PBP3)transpeptidase

β-lactams and related drugs inhibit PBPs by covalent acylation, blocking transpeptidase activity, thereby preventing peptidoglycan cross-linking and leading to cell lysis Some drugs also inhibit glycosyltransferase activity (where present) Metal chelators may inhibit Zn-dependent PBPs (new strategy)