On the role of the high molecular weight penicillin-binding proteins in the cell cycle of Escherichia coli.
Blocking of penicillin-binding proteins (PBP) 2 or 3 of Escherichia coli by specific antibiotics led to inhibition of peptidoglycan synthesis measured as rate of 3H-Dap incorporation. The inhibition was ca 60% by mecillinam (blocking PBP2) and ca 35% by cephalexin or furazlocillin (both specific for PBP3). PBP3 could be inhibited primarily during constriction, whereas the inhibition of PBP2 was observed throughout the cell cycle. The ratio of PBP2 and 3 activities appeared to be correlated with cell shape, i.e. in long rods, inhibition of peptidoglycan synthesis by mecillinam was stronger than in short rods. Inhibition studies with the PBP1A/1B-specific antibiotic cefsulodin showed that, with a delay of approximately 1/2 mass-doubling time, peptidoglycan synthesis was inhibited completely with concomitant lysis. The cefsulodin-induced lysis was independent of the stage of the cell cycle. It was suggested that PBP1A/1B do not have a specific function in either elongation or constriction. Rather, they seem to have a general activity on the basis of which the other synthesizing PBP perform their special tasks. This interpretation is formulated as a "primer model of peptidoglycan synthesis".
Department of Molecular Cell Biology, University of Amsterdam.
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Wientjes
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Nanninga
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010457:Peptidoglycan; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase