PDF(Pubmed)
Abstract：
Peptidoglycan (PG) is an important architectural element that imparts physical toughness and rigidity to the bacterial envelope. It is also a dynamic structure that undergoes continuous turnover or autolysis. Escherichia coli possesses redundant PG degradation enzymes responsible for PG turnover; however, the advantage afforded by the existence of numerous PG degradation enzymes remains incompletely understood. In this study, we elucidated the physiological roles of MltE and MltC, members of the lytic transglycosylase (LTG) family that catalyze the cleavage of glycosidic bonds between disaccharide subunits within PG strands. MltE and MltC are acidic LTGs that exhibit increased enzymatic activity and protein levels under acidic pH conditions, respectively, and deletion of these two LTGs results in a pronounced growth defect at acidic pH. Furthermore, inactivation of these two LTGs induces increased susceptibility at acidic pH against various antibiotics, particularly vancomycin, which seems to be partially caused by elevated membrane permeability. Intriguingly, inactivation of these LTGs induces a chaining morphology, indicative of daughter cell separation defects, only under acidic pH conditions. Simultaneous deletion of PG amidases, known contributors to daughter cell separation, exacerbates the chaining phenotype at acidic pH. This suggests that the two LTGs may participate in the cleavage of glycan strands between daughter cells under acidic pH conditions. Collectively, our findings highlight the role of LTG repertoire diversity in facilitating bacterial survival and antibiotic resistance under stressful conditions.
摘要：
肽聚糖（PG）是一种重要的建筑元素，可赋予细菌外壳物理韧性和刚性。它也是经历连续周转或自溶的动态结构。大肠杆菌具有负责PG周转的冗余PG降解酶；然而，许多PG降解酶的存在所提供的优势仍未被完全理解。在这项研究中,我们阐明了mltE和mltC的生理作用，裂解转糖基酶（LTG）家族的成员，催化PG链内二糖亚基之间的糖苷键的裂解。MltE和MltC是酸性LTGs，在酸性pH条件下表现出增加的酶活性和蛋白质水平，分别,并且这两个LTGs的缺失导致在酸性pH下明显的生长缺陷。此外，这两种LTGs的失活诱导在酸性pH下对各种抗生素的敏感性增加，尤其是万古霉素,这似乎部分是由膜通透性升高引起的。有趣的是，这些LTGs的失活诱导连锁形态，指示子细胞分离缺陷，仅在酸性pH条件下。同时删除PG酰胺酶，已知子细胞分离的贡献者，在酸性pH下加剧链接表型。这表明在酸性pH条件下,两个LTG可参与子细胞之间的聚糖链的裂解。总的来说，我们的研究结果强调了LTG库多样性在应激条件下促进细菌存活和抗生素耐药性的作用.
