New secreted toxins and immunity proteins encoded within the Type VI secretion system gene cluster of Serratia marcescens.
New secreted toxins and immunity proteins encoded within the Type VI secretion system gene cluster of Serratia marcescens.
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DOI：
10.1111/mmi.12028
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发表时间：
2012-11
影响因子：
3.6
通讯作者：
Coulthurst SJ
中科院分区：
文献类型：
--
作者：
English G;Trunk K;Rao VA;Srikannathasan V;Hunter WN;Coulthurst SJ
蛋白质分泌系统对于细菌毒力以及与其他生物体的相互作用至关重要。 VI 型分泌系统 (T6SS) 存在于许多细菌物种中，用于靶向真核细胞或竞争细菌。然而，T6SS 分泌蛋白已被证明令人惊讶地难以捉摸。在这里，我们从机会性人类病原体粘质沙雷氏菌中鉴定出抗菌 T6SS 的两种分泌底物。 Ssp1 和 Ssp2 均在 T6SS 基因簇内编码，被证实是 T6SS 传递的抗菌毒素。 Ssp 蛋白（“Rap”蛋白）周围编码的四种相关蛋白包括两种专门赋予针对 T6SS 依赖性 Ssp1 或 Ssp2 毒性的自我抵抗（“免疫”）的蛋白。生化表征揭示了同源 Ssp-Rap 对之间特异性、紧密的结合，形成 2:2 化学计量的复合物。两种 Rap 蛋白的原子结构得到解决，揭示了一种依赖于结构二硫键的新型螺旋折叠，这种结构特征与其功能定位一致。沙雷氏菌 Ssp 和 Rap 蛋白的同源物被发现在其他 T6SS 基因簇中一起编码，因此它们代表了 T6SS 分泌和同源免疫蛋白新家族的创始人成员。我们认为，在水平获取其他 T6SS 分泌的毒素之前，Ssp 蛋白是粘质链球菌 T6SS 的原始底物。病原体如何利用抗菌 T6SS 来克服竞争对手并在多种微生物领域取得成功，已经提供了分子见解。
Protein secretion systems are critical to bacterial virulence and interactions with other organisms. The Type VI secretion system (T6SS) is found in many bacterial species and is used to target either eukaryotic cells or competitor bacteria. However, T6SS-secreted proteins have proven surprisingly elusive. Here, we identified two secreted substrates of the antibacterial T6SS from the opportunistic human pathogen, Serratia marcescens. Ssp1 and Ssp2, both encoded within the T6SS gene cluster, were confirmed as antibacterial toxins delivered by the T6SS. Four related proteins encoded around the Ssp proteins (‘Rap’ proteins) included two specifically conferring self-resistance (‘immunity’) against T6SS-dependent Ssp1 or Ssp2 toxicity. Biochemical characterization revealed specific, tight binding between cognate Ssp–Rap pairs, forming complexes of 2:2 stoichiometry. The atomic structures of two Rap proteins were solved, revealing a novel helical fold, dependent on a structural disulphide bond, a structural feature consistent with their functional localization. Homologues of the Serratia Ssp and Rap proteins are found encoded together within other T6SS gene clusters, thus they represent founder members of new families of T6SS-secreted and cognate immunity proteins. We suggest that Ssp proteins are the original substrates of the S. marcescens T6SS, before horizontal acquisition of other T6SS-secreted toxins. Molecular insight has been provided into how pathogens utilize antibacterial T6SSs to overcome competitors and succeed in polymicrobial niches.
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影响因子：
30.3
作者：
Jani AJ;Cotter PA
通讯作者：
Cotter PA
影响因子：
3.1
作者：
Aubert, Daniel F.;Flannagan, Ronald S.;Valvano, Miguel A.
通讯作者：
Valvano, Miguel A.
影响因子：
6.7
作者：
Li M;Le Trong I;Carl MA;Larson ET;Chou S;De Leon JA;Dove SL;Stenkamp RE;Mougous JD
通讯作者：
Mougous JD
影响因子：
14.9
作者：
Laskowski RA;Watson JD;Thornton JM
通讯作者：
Thornton JM
影响因子：
3.2
作者：
Murdoch, Sarah L.;Trunk, Katharina;Coulthurst, Sarah J.
通讯作者：
Coulthurst, Sarah J.