Interference with murein turnover has no effect on growth but reduces β-lactamase induction in Escherichia coli
Interference with murein turnover has no effect on growth but reduces β-lactamase induction in Escherichia coli
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DOI：
10.1128/jb.181.23.7192-7198.1999
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发表时间：
1999-12-01
影响因子：
3.2
通讯作者：
Höltje, JV
中科院分区：
文献类型：
--
作者：
Kraft, AR;Prabhu, J;Höltje, JV
对缺乏三种裂解性转糖基酶 Slt70、MltA 和 MltB 的大肠杆菌突变体的生理研究表明，干扰胞壁质周转可以阻止 AmpC β-内酰胺酶的诱导。三重突变体虽然生长正常，但显示胞壁质周转率显着降低。尽管低分子量壁质周转产物的形成减少，但壁质合成速率和每个细胞的壁质数量均未增加。这可以通过假设在不存在主要裂解性转糖基酶的情况下生长期间，天然胞壁质链被内肽酶的作用切除并直接重新使用而不会进一步分解为胞壁肽来解释。胞壁蛋白周转率的降低可能与头孢西丁诱导的β-内酰胺酶表达降低有关，该酶存在于携带来自阴沟杆菌的ampC和ampR基因的质粒上。MltB的过量产生刺激了β-内酰胺酶的诱导，而bulgecin对Slt70的特异性抑制抑制了ampC表达。因此，裂解性转糖基酶的特异性抑制剂可以增加青霉素和头孢菌素针对诱导 AmpC 样 β-内酰胺酶的细菌的效力。
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.