Effect of mecillinam on peptidoglycan synthesis during the division cycle of Salmonella typhimurium 2616.
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.
Licht
J
J
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620.
Gally
D
D
Henderson
T
T
Young
K
K
Cooper
S
S
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
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