Compound-gene interaction mapping reveals distinct roles for Staphylococcus aureus teichoic acids
Compound-gene interaction mapping reveals distinct roles for Staphylococcus aureus teichoic acids
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DOI：
10.1073/pnas.1404099111
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发表时间：
2014-08-26
影响因子：
11.1
通讯作者：
Walker, Suzanne
中科院分区：
文献类型：
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作者：
Maria, John P. Santa, Jr.;Sadaka, Ama;Walker, Suzanne
金黄色葡萄球菌含有两种不同的磷壁酸（TA）聚合物，脂磷壁酸（LTA）和壁磷壁酸（WTA），它们被认为在调节细胞分裂中起着冗余的作用。为了深入了解S.为了检测金黄色葡萄球菌TA，我们使用小分子抑制剂来筛选高度饱和的转座子文库，以获得当WTA耗尽时变得必需的细胞因子。我们构建了一个将WTA与参与LTA合成、肽聚糖合成、表面蛋白展示和D-丙氨酸细胞包膜修饰的基因连接起来的相互作用网络。虽然LTA和WTA是合成致死的，我们报告说，他们没有相同的合成与其他细胞包膜基因的相互作用。例如，D-丙氨酰化是WTA和LTA的一种定制修饰，当前者而不是后者被去除时，它就变得至关重要。因此，当不存在WTA时，需要D-丙氨酸定制的LTA才能生存。对末端表型的检查导致了意外的发现，即缺乏LTA和WTA的细胞失去了形成Z环的能力，并且不能再分裂。我们的结论是，无论是在细胞表面的LTA或WTA的存在是需要启动S。金黄色葡萄球菌细胞分裂，但这些聚合物作为不同的细胞网络的一部分。
Staphylococcus aureus contains two distinct teichoic acid ( TA) polymers, lipoteichoic acid (LTA) and wall teichoic acid (WTA), which are proposed to play redundant roles in regulating cell division. To gain insight into the underlying biology of S. aureus TAs, we used a small molecule inhibitor to screen a highly saturated transposon library for cellular factors that become essential when WTA is depleted. We constructed an interaction network connecting WTAs with genes involved in LTA synthesis, peptidoglycan synthesis, surface protein display, and D-alanine cell envelope modifications. Although LTAs and WTAs are synthetically lethal, we report that they do not have the same synthetic interactions with other cell envelope genes. For example, D-alanylation, a tailoring modification of both WTAs and LTAs, becomes essential when the former, but not the latter, are removed. Therefore, D-alanine-tailored LTAs are required for survival when WTAs are absent. Examination of terminal phenotoypes led to the unexpected discovery that cells lacking both LTAs and WTAs lose their ability to form Z rings and can no longer divide. We have concluded that the presence of either LTAs or WTAs on the cell surface is required for initiation of S. aureus cell division, but these polymers act as part of distinct cellular networks.