All β-lactams share the same mode of action: they inhibit the bacterial cell wall synthesis by acting
as suicide substrates of the transpeptidase domain of Penicillin Binding Proteins (PBPs). They form a
stable covalent adduct with the active site serine residue of PBPs (Figure 2). The PBPs are traditionally
partitioned into high molecular weight PBPs (HMW-PBPs), which are further divided in two classes,
A and B, and low-molecular weight PBPs (LMW-PBPs), which are also divided in four subclasses
based on their tertiary structures. HMW-PBPs are essential to cell survival and are the actual target
of β-lactams. Class A PBPs catalyze the formation of the glycan chains (trans-glycosylation) and both
class A and class B PBPs catalyze the cross-linking of peptidoglycan stem-peptides (transpeptidation)
on the external side of the cytoplasmic membrane. Peptidoglycan is specific to bacteria and drugs
which inhibit its biosynthesis have low toxicity to humans. LMW-PBPs are dispensable in laboratory
conditions and thus represent minor targets of β-lactam antibiotics.