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, consisting of five glycine residues. The femAB operon, coding for two approximately 50-kDa proteins is known to be involved in pentaglycine bridge formation. Using chemical mutagenesis of the beta-lactam-resistant strain BB270 and genetic, biochemical, and biophysical characterization of mutants selected for loss of beta-lactam resistance and reduced lysostaphin sensitivity it is shown that peptide bridge formation proceeds via three intermediate bridge lengths (cell wall peptides with no, one, three, and five glycine units). To proceed from one intermediate to the next, three genes appear necessary: femX, femA, and femB. The drastic loss of beta-lactam resistance after inactivation of FemA or partial impairment of FemX even beyond the level of the sensitive wild-type strains renders these proteins attractive antistaphylococcal targets.
Kopp
U
U
Bayer AG, Pharma Research Antiinfectives I, Wuppertal, Germany.
Roos
M
M
Wecke
J
J
Labischinski
H
H
D000596:Amino Acids / Q000032:analysis; D001426:Bacterial Proteins / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002473:Cell Wall / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D018274:Electroporation; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D016296:Mutagenesis / Q000187:drug effects; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018440:beta-Lactam Resistance
D000596:Amino Acids; D001426:Bacterial Proteins; D003432:Cross-Linking Reagents; D004269:DNA, Bacterial; C096686:FemA protein, Bacteria; C102928:FemB protein, Staphylococcus epidermidis; D010457:Peptidoglycan