A murein hydrolase is the specific target of bulgecin in Escherichia coli.
A deletion in the structural gene for the soluble lytic transglycosylase, the predominant murein hydrolase in the soluble fraction of Escherichia coli, has been constructed. The mutant grows normally but exhibits increased sensitivity toward mecillinam, a beta-lactam specific for penicillin-binding protein 2. In the presence of furazlocillin or other beta-lactams with a specificity for penicillin-binding protein 3 which normally cause filamentation, bulges were formed prior to rapid bacteriolysis. Similar morphological alterations are known to develop in wild type E. coli cells when furazlocillin is combined with bulgecin, an antibiotic of unusual glucosaminyl structure. It turned out that bulgecin specifically inhibits the Sl-transglycosylase in a noncompetitive manner. Since bulgecin shows some structural analogy to the murein subunits we postulate that the soluble lytic transglycosylase, in addition to its active site, has a recognition site for specific murein structures. The possibility of an allosteric modulation of the activity of the enzyme by changes in the structure of the murein sacculus is discussed.
Templin
M F
MF
Max-Planck Institut für Entwicklungsbiologie, Abteilung Biochemie, Tübingen, Germany.
Edwards
D H
DH
Höltje
J V
JV
D000560:Amdinocillin / Q000494:pharmacology; D001390:Azlocillin / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017353:Gene Deletion; D005798:Genes, Bacterial; D006020:Glycopeptides / Q000378:metabolism*; D016695:Glycosyltransferases; D048289:Imidazolidines; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013379:Substrate Specificity; D014166:Transferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D006020:Glycopeptides; D048289:Imidazolidines; C036713:bulgecin; D014166:Transferases; D016695:Glycosyltransferases; C021815:murein transglycosylase; D001390:Azlocillin; C017976:furazlocillin; D000560:Amdinocillin