STAPHYLOCOCCAL PEPTIDOGLYCAN INTERPEPTIDE BRIDGE BIOSYNTHESIS - A NOVEL ANTISTAPHYLOCOCCAL TARGET

In staphylococci, crosslinking of the peptide moiety of peptidoglycan is mediated via an additional spacer, the interpeptide bridge, consist ing of five glycine residues, The femAB operon, coding for two similar to 50-kDa proteins is known to be involved in pentaglycine bridge for mation, Using chemical mutagenesis of the beta-lactam-resistant strain BB270 and genetic, biochemical, and biophysical characterization of m utants selected for loss of beta-lactam resistance and reduced lysosta phin sensitivity it is shown that peptide bridge formation proceeds vi a three intermediate bridge lengths (cell wall peptides with no, one, three, and five glycine units), To proceed from one intermediate to th e next, three genes appear necessary: femX, femA, and femB, The drasti c loss of beta-lactam resistance after inactivation of FemA or partial impairment of FemX even beyond the level of the sensitive wild-type s trains renders these proteins attractive antistaphylococcal targets.