Interference with murein turnover has no effect on growth but reduces beta-lactamase induction in Escherichia coli.
Physiological studies of a mutant of Escherichia coli lacking the three lytic transglycosylases Slt70, MltA, and MltB revealed that interference with murein turnover can prevent AmpC beta-lactamase induction. The triple mutant, although growing normally, shows a dramatically reduced rate of murein turnover. Despite the reduction in the formation of low-molecular-weight murein turnover products, neither the rate of murein synthesis nor the amount of murein per cell was increased. This might be explained by assuming that during growth in the absence of the major lytic transglycosylases native murein strands are excised by the action of endopeptidases and directly reused without further breakdown to muropeptides. The reduced rate of murein turnover could be correlated with lowered cefoxitin-induced expression of beta-lactamase, present on a plasmid carrying the ampC and ampR genes from Enterobacter cloacae. Overproduction of MltB stimulated beta-lactamase induction, whereas specific inhibition of Slt70 by bulgecin repressed ampC expression. Thus, specific inhibitors of lytic transglycosylases can increase the potency of penicillins and cephalosporins against bacteria inducing AmpC-like beta-lactamases.
Kraft
A R
AR
Abteilung Biochemie, Max-Planck-Institut für Entwicklungsbiologie, 72076 Tübingen, Germany.
Prabhu
J
J
Ursinus
A
A
Höltje
J V
JV
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016972:Enterobacter cloacae / Q000201:enzymology; D004789:Enzyme Activation / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000254:growth & development; D029968:Escherichia coli Proteins; D006026:Glycoside Hydrolases; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010457:Peptidoglycan / Q000378:metabolism*; D013997:Time Factors; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000378:metabolism*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D010457:Peptidoglycan; D016695:Glycosyltransferases; C085441:MltA protein, bacteria; C021815:murein transglycosylase; D006026:Glycoside Hydrolases; C085428:slt protein, E coli; C048795:AmpC beta-lactamases; D001618:beta-Lactamases