Spatial regulation of protein A in Staphylococcus aureus.
Spatial regulation of protein A in Staphylococcus aureus.
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DOI：
10.1111/mmi.14734
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发表时间：
2021-08
影响因子：
3.6
通讯作者：
Yu W
中科院分区：
文献类型：
--
作者：
Zhang R;Shebes MA;Kho K;Scaffidi SJ;Meredith TC;Yu W
金黄色葡萄球菌表面蛋白在细菌生理和致病机制中起着重要作用。最近的工作表明，表面蛋白受YSIRK/GXXS信号肽的空间调控，该信号肽促进跨壁靶向中间细胞，尽管机制尚不清楚。我们以前已经证明，蛋白A(SpA)是一种YSIRK/GXXS蛋白，也是金黄色葡萄球菌的关键毒力因子，它错误地定位于脂磷壁酸(LTA)产生缺陷的ltas突变体。在这里，我们发现SpA含有另一个跨壁靶向信号，LysM结构域，除了YSIRK/GXXS信号肽外，它还能显著增强SPA的跨壁靶向。我们表明，温泉隔锚和跨壁沉积需要LTA合成，而不是LTA。有趣的是，LTA主要发现在外周细胞膜上，在分裂葡萄球菌细胞的隔膜上减少，这表明SpA隔膜定位的限制机制。最后，我们证明了LTA的D-丙氨酸化通过破坏SpA在肽聚糖层中的分布而不改变SpA的隔膜锚定，从而取消了SpA的跨壁沉积。我们的研究表明，多种因素通过不同的机制参与SpA的空间调控和跨壁靶向，从而确保在细胞周期中表面蛋白有效地整合到正在生长的肽聚糖中。
Surface proteins of Staphylococcus aureus play vital roles in bacterial physiology and pathogenesis. Recent work suggests that surface proteins are spatially regulated by a YSIRK/GXXS signal peptide that promotes cross-wall targeting at the mid-cell, though the mechanisms remain unclear. We previously showed that protein A (SpA), a YSIRK/GXXS protein and key staphylococcal virulence factor, mis-localizes in a ltaS mutant deficient in lipoteichoic acid (LTA) production. Here, we identified that SpA contains another cross-wall targeting signal, the LysM domain, which, in addition to the YSIRK/GXXS signal peptide, significantly enhances SpA cross-wall targeting. We show that LTA synthesis, but not LtaS, is required for SpA septal anchoring and cross-wall deposition. Interestingly, LTA is predominantly found at the peripheral cell membrane and is diminished at the septum of dividing staphylococcal cells, suggesting a restriction mechanism for SpA septal localization. Finally, we show that D-alanylation of LTA abolishes SpA cross-wall deposition by disrupting SpA distribution in the peptidoglycan layer without altering SpA septal anchoring. Our study reveals that multiple factors contribute to the spatial regulation and cross-wall targeting of SpA via different mechanisms, which coordinately ensures efficient incorporation of surface proteins into the growing peptidoglycan during the cell cycle.
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影响因子：
6.4
作者：
Bæk KT;Bowman L;Millership C;Dupont Søgaard M;Kaever V;Siljamäki P;Savijoki K;Varmanen P;Nyman TA;Gründling A;Frees D
通讯作者：
Frees D
影响因子：
4.8
作者：
Frankel, Matthew B.;Schneewind, Olaf
通讯作者：
Schneewind, Olaf
DOI：
10.1073/pnas.1004304107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Atilano, Magda L.;Pereira, Pedro M.;Filipe, Sergio R.
通讯作者：
Filipe, Sergio R.
影响因子：
3.2
作者：
Grundling, Angelika;Schneewind, Olaf
通讯作者：
Schneewind, Olaf
影响因子：
3.6
作者：
Jonquières, R;Bierne, H;Cossart, P
通讯作者：
Cossart, P