Discrete and overlapping functions of peptidoglycan synthases in growth, cell division and virulence of Listeria monocytogenes.
Discrete and overlapping functions of peptidoglycan synthases in growth, cell division and virulence of Listeria monocytogenes.
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DOI：
10.1111/mmi.12873
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发表时间：
2015-01
影响因子：
3.6
通讯作者：
Halbedel S
中科院分区：
文献类型：
--
作者：
Rismondo J;Möller L;Aldridge C;Gray J;Vollmer W;Halbedel S
在摄入受污染的食物后，单核细胞增生李斯特菌可导致人类严重感染，通常用β-内酰胺抗生素治疗。这些靶向李斯特菌的五种高分子量青霉素结合蛋白（HMW PBP），这是肽聚糖生物合成所需的。两种双功能A类HMW PBPs PBP A1和PBP A2分别具有催化聚糖链聚合和肽交联的转糖基酶和转肽酶结构域，而三种B类HMW PBPs B1、B2和B3是单功能转肽酶。这些PBP在细胞周期中的确切作用尚不清楚。在这里，我们表明，绿色荧光蛋白（GFP）-PBP融合定位于无论是在隔膜，侧壁或两者，这表明不同的和重叠的功能。遗传数据证实了这一观点：PBP A1和PBP A2不能同时失活，条件双突变株在很大程度上依赖于诱导剂。PBP B1是杆状所必需的，PBP B2是跨壁生物合成和活力所必需的，而PBP B3是生长和细胞分裂所必需的。PBP B1消耗显著增加β-内酰胺的亲合性并刺激自发自溶，但对肽聚糖交联没有影响。我们的体外毒力测定表明，所有HMW PBPs的完整集合是最大毒力所必需的。
Upon ingestion of contaminated food, Listeria monocytogenes can cause serious infections in humans that are normally treated with β-lactam antibiotics. These target Listeria's five high molecular weight penicillin-binding proteins (HMW PBPs), which are required for peptidoglycan biosynthesis. The two bi-functional class A HMW PBPs PBP A1 and PBP A2 have transglycosylase and transpeptidase domains catalyzing glycan chain polymerization and peptide cross-linking, respectively, whereas the three class B HMW PBPs B1, B2 and B3 are monofunctional transpeptidases. The precise roles of these PBPs in the cell cycle are unknown. Here we show that green fluorescent protein (GFP)-PBP fusions localized either at the septum, the lateral wall or both, suggesting distinct and overlapping functions. Genetic data confirmed this view: PBP A1 and PBP A2 could not be inactivated simultaneously, and a conditional double mutant strain is largely inducer dependent. PBP B1 is required for rod-shape and PBP B2 for cross-wall biosynthesis and viability, whereas PBP B3 is dispensable for growth and cell division. PBP B1 depletion dramatically increased β-lactam susceptibilities and stimulated spontaneous autolysis but had no effect on peptidoglycan cross-linkage. Our in vitro virulence assays indicated that the complete set of all HMW PBPs is required for maximal virulence.
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影响因子：
3.6
作者：
Bergmann, B;Raffelsbauer, D;Goebel, W
通讯作者：
Goebel, W
影响因子：
3.6
作者：
Jonquières, R;Bierne, H;Cossart, P
通讯作者：
Cossart, P
影响因子：
2.9
作者：
Bui, Nhat Khai;Eberhardt, Alice;Vollmer, Waldemar
通讯作者：
Vollmer, Waldemar
影响因子：
3.2
作者：
CHAKRABORTY, T;LEIMEISTERWACHTER, M;NOTERMANS, S
通讯作者：
NOTERMANS, S
影响因子：
3.6
作者：
Cabanes, D;Dussurget, O;Cossart, P
通讯作者：
Cossart, P