Colicin M is an enzymatic bacteriocin produced by some Escherichia coli strains which provokes cell lysis of competitor strains by hydrolysis of the cell wall peptidoglycan undecaprenyl-PP-MurNAc(-pentapeptide)-GlcNAc (lipid II) precursor. The overexpression of a gene, cbrA (formerly yidS), was shown to protect E. coli cells from the deleterious effects of this colicin, but the underlying resistance mechanism was not established. We report here that a major structural modification of the undecaprenyl-phosphate carrier lipid and of its derivatives occurred in membranes of CbrA-overexpressing cells, which explains the acquisition of resistance toward this bacteriocin. Indeed, a main fraction of these lipids, including the lipid II peptidoglycan precursor, now displayed a saturated isoprene unit at the α-position, i.e., the unit closest to the colicin M cleavage site. Only unsaturated forms of these lipids were normally detectable in wild-type cells. In vitro and in vivo assays showed that colicin M did not hydrolyze α-saturated lipid II, clearly identifying this substrate modification as the resistance mechanism. These saturated forms of undecaprenyl-phosphate and lipid II remained substrates of the different enzymes participating in peptidoglycan biosynthesis and carrier lipid recycling, allowing this colicin M-resistance mechanism to occur without affecting this essential pathway.

中文翻译：

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CbrA通过修饰十一碳烯基磷酸酯连接的肽聚糖前体来介导大肠杆菌中的大肠菌素M抗性。

Colicin M是由一些大肠杆菌菌株产生的酶促细菌素，可通过水解细胞壁肽聚糖十一碳烯基-PP-MurNAc（-五肽）-GlcNAc（脂质II）前体来激发竞争性菌株的细胞裂解。基因过表达cbrA（以前为yidS），可以保护大肠杆菌。细胞不受此菌素的有害作用，但尚未建立潜在的耐药机制。我们在这里报告，十一碳烯基磷酸载体脂质及其衍生物的主要结构修饰发生在CbrA过表达细胞的膜中，这解释了对这种细菌素的抗性的获得。实际上，这些脂质的主要部分，包括脂质II肽聚糖前体，现在在α位置显示了一个饱和的异戊二烯单元，即最接近大肠菌素M裂解位点的单元。通常在野生型细胞中只能检测到这些脂质的不饱和形式。体外和体内分析表明大肠菌素M不会水解α-饱和脂质II，清楚地确定了这种底物修饰是抗药性机制。这些饱和形式的十一碳烯基磷酸酯和脂质II仍然是参与肽聚糖生物合成和载体脂质再循环的不同酶的底物，从而使这种大肠菌素M抗性机制得以发生而不会影响该基本途径。