Lytic transglycosylases LtgA and LtgD perform distinct roles in remodeling, recycling and releasing peptidoglycan in Neisseria gonorrhoeae
Lytic transglycosylases LtgA and LtgD perform distinct roles in remodeling, recycling and releasing peptidoglycan in Neisseria gonorrhoeae
复制标题
DOI：
10.1111/mmi.13496
复制
发表时间：
2016-12-01
影响因子：
3.6
通讯作者：
Dillard, Joseph P.
中科院分区：
文献类型：
--
作者：
Schaub, Ryan E.;Chan, Yolande A.;Dillard, Joseph P.
淋病奈瑟菌在感染期间释放肽聚糖（PG）片段，其引起大的炎症反应，并且在盆腔炎性疾病中，该反应导致输卵管纤毛细胞的死亡和脱落。我们的特点的生化功能和本地化的两种酶负责释放促炎性PG片段。推定的裂解转糖基酶LtgA和LtgD显示产生1，6-脱水胞壁酰部分，并且两种酶都能够将小的合成四糖二肽PG片段消化成同源的含1，6-脱水胞壁酰的反应产物。LtgA降解四糖PG片段是第一次证明了家族1裂解转糖基酶表现出这种活性。淋球菌中的脉冲追踪实验表明，LtgA比LtgD产生更大量的PG片段，并且这些片段中的绝大多数被回收。相反，LtgD是必需的野生型水平的PG前体掺入和产生的片段主要从细胞释放。此外，超分辨率显微镜确定LtgA定位于隔膜，而LtgD定位于细胞周围。这项研究提出了一个模型，其中LtgD产生PG单体的方式，这些片段被释放，而LtgA创建的片段，主要是进入细胞质回收。
Neisseria gonorrhoeae releases peptidoglycan (PG) fragments during infection that provoke a large inflammatory response and, in pelvic inflammatory disease, this response leads to the death and sloughing of ciliated cells of the Fallopian tube. We characterized the biochemical functions and localization of two enzymes responsible for the release of proinflammatory PG fragments. The putative lytic transglycosylases LtgA and LtgD were shown to create the 1,6-anhydromuramyl moieties, and both enzymes were able to digest a small, synthetic tetrasaccharide dipeptide PG fragment into the cognate 1,6-anhydromuramyl-containing reaction products. Degradation of tetrasaccharide PG fragments by LtgA is the first demonstration of a family 1 lytic transglycosylase exhibiting this activity. Pulse-chase experiments in gonococci demonstrated that LtgA produces a larger amount of PG fragments than LtgD, and a vast majority of these fragments are recycled. In contrast, LtgD was necessary for wild-type levels of PG precursor incorporation and produced fragments predominantly released from the cell. Additionally, super-resolution microscopy established that LtgA localizes to the septum, whereas LtgD is localized around the cell. This investigation suggests a model where LtgD produces PG monomers in such a way that these fragments are released, whereas LtgA creates fragments that are mostly taken into the cytoplasm for recycling.