A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules.
A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules.
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DOI：
10.1021/cb100195d
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发表时间：
2010-12-17
影响因子：
4
通讯作者：
Spiegel, David A.
中科院分区：
文献类型：
--
作者：
Nelson, James W.;Chamessian, Alexander G.;McEnaney, Patrick J.;Murelli, Ryan P.;Kazmiercak, Barbara I.;Spiegel, David A.
金黄色葡萄球菌(S.金黄色葡萄球菌）是一种革兰氏阳性细菌病原体，已经成为主要的公共健康威胁。本文报道了S.金黄色葡萄球菌可被共价重组以包含非天然小分子。该过程利用了细菌酶分类酶A（SrtA）的内源水平，其通常的功能是将蛋白质掺入细菌细胞壁中。因此，将野生型细菌与合理设计的SrtA底物一起孵育，导致功能性分子柄（荧光素、生物素和叠氮化物）共价掺入细胞壁肽聚糖中。这些结论得到了通过多种实验技术（落射荧光和电子显微镜、生化提取和质谱）获得的数据的支持，并且叠氮化物掺入被用作在细菌细胞表面进行叠氮化物-炔烃环加成反应的化学处理。本研究首次报道了S.金黄色葡萄球菌或任何其它致病性革兰氏阳性细菌，并具有广泛应用的潜力。
Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (SrtA), which ordinarily functions to incorporate proteins into the bacterial cell wall. Thus, incubation of wild-type bacteria with rationally designed SrtA substrates results in covalent incorporation of functional molecular handles (fluorescein, biotin, and azide) into cell wall peptidoglycan. These conclusions are supported by data obtained through a variety of experimental techniques (epifluorescence and electron microscopy, biochemical extraction, and mass spectrometry), and azide incorporation was exploited as a chemical handle to perform an azide-alkyne cycloaddition reaction on the bacterial cell surface. This report represents the first example of cell wall engineering of S. aureus or any other pathogenic Gram-positive bacteria, and has the potential for widespread utility.
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影响因子：
15
作者：
Murelli, Ryan P.;Zhang, Andrew X.;Michel, Julien;Jorgensen, William L.;Spiegel, David A.
通讯作者：
Spiegel, David A.
DOI：
10.1073/pnas.080520697
发表时间：
2000-05-09
影响因子：
11.1
作者：
Mazmanian, SK;Liu, G;Schneewind, O
通讯作者：
Schneewind, O
影响因子：
4
作者：
Carlson, Coby B.;Mowery, Patricia;Kiessling, Laura L.
通讯作者：
Kiessling, Laura L.
影响因子：
4.7
作者：
Parthasarathy, Ranganath;Subramanian, Shyamsundar;Boder, Eric T.
通讯作者：
Boder, Eric T.
影响因子：
120.7
作者：
Klevens, R. Monina;Morrison, Melissa A.;Fridkin, Scott K.
通讯作者：
Fridkin, Scott K.