title: Effect of mecillinam on peptidoglycan synthesis during the division cycle of Salmonella typhimurium 2616.
abstract: The effects of mecillinam, ampicillin and cephalexin on peptidoglycan synthesis in Salmonella typhimurium 2616 have been studied at equivalent concentrations or "isoactivities". Using antibiotics at isoactivities allows a direct comparison of the biochemical effects of different antibiotics. When mecillinam was added at different times during the division cycle at a concentration that produced 50% inhibition of peptidoglycan synthesis in an exponential culture over a short period of time, the inhibition of synthesis was greatest in the newborn cells and least in the dividing cells. Antibiotic competition experiments showed that mecillinam preferentially bound to penicillin-binding protein 2 in S. typhimurium 2616. High performance liquid chromatography analysis of the residual peptidoglycan synthesized in the presence of mecillinam showed an unexpected increase in pentapeptides and a significant increase in cross-linking. Other antibiotics added at equivalent activities did not show an increase in cross-linking.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620.
authors.forename: J
authors.initials: J
authors.lastname: Licht
authors.forename: D
authors.initials: D
authors.lastname: Gally
authors.forename: T
authors.initials: T
authors.lastname: Henderson
authors.forename: K
authors.initials: K
authors.lastname: Young
authors.forename: S
authors.initials: S
authors.lastname: Cooper
mesh_terms: D000560:Amdinocillin / Q000494:pharmacology*; D000667:Ampicillin / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects*; D002506:Cephalexin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003864:Depression, Chemical; D006602:Hexosyltransferases / Q000378:metabolism; D066298:In Vitro Techniques; D009097:Multienzyme Complexes / Q000378:metabolism; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000032:analysis / Q000096:biosynthesis*; D010458:Peptidyl Transferases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D000667:Ampicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002506:Cephalexin; D000560:Amdinocillin