RpoN/Sfa2-dependent activation of the Pseudomonas aeruginosa H2-T6SS and its cognate arsenal of antibacterial toxins.
RpoN/Sfa2-dependent activation of the Pseudomonas aeruginosa H2-T6SS and its cognate arsenal of antibacterial toxins.
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DOI：
10.1093/nar/gkab1254
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发表时间：
2022-01-11
影响因子：
14.9
通讯作者：
Filloux A
中科院分区：
文献类型：
--
作者：
Allsopp LP;Collins ACZ;Hawkins E;Wood TE;Filloux A
铜绿假单胞菌（Pseudomonasaeruginosa）利用三种六型分泌系统（H1-、H2-和H3-T6 SS）来操纵其环境、颠覆宿主细胞和进行微生物竞争。这些T6 SS机器装载有各种效应物/毒素，许多与特定的VgrG相关。铜绿假单胞菌如何在转录上协调主要的T6 SS簇和通过基因组散布的多个vgrG岛是未知的。在这里，我们展示了RsmA抑制大多数已知的T6 SS相关基因的前所未有的控制水平。此外，H2-和H3-T6 SS簇中的每一个分别编码称为Sfa 2和Sfa 3的σ因子激活剂（SFA）蛋白。SFA蛋白是σ因子RpoN所必需的增强子结合蛋白。使用RNA-seq，ChIP-seq和分子生物学方法的组合，我们证明RpoN通过激活H2-T6 SS但抑制H1-和H3-T6 SS来协调铜绿假单胞菌的T6 SS。此外，RpoN和Sfa 2控制H2-T6 SS连接的VgrG及其效应子库的表达，以实现非常有效的细菌间杀伤。Sfa 2是特异性的，因为来自H3-T6 SS的Sfa 3不能补充Sfa 2的缺失。我们的研究进一步描述了调节T6 SS效应子库部署的调控机制，这些效应子可能使铜绿假单胞菌适应一系列环境条件。
Pseudomonas aeruginosa uses three type six secretion systems (H1-, H2- and H3-T6SS) to manipulate its environment, subvert host cells and for microbial competition. These T6SS machines are loaded with a variety of effectors/toxins, many being associated with a specific VgrG. How P. aeruginosa transcriptionally coordinates the main T6SS clusters and the multiple vgrG islands spread through the genome is unknown. Here we show an unprecedented level of control with RsmA repressing most known T6SS-related genes. Moreover, each of the H2- and H3-T6SS clusters encodes a sigma factor activator (SFA) protein called, Sfa2 and Sfa3, respectively. SFA proteins are enhancer binding proteins necessary for the sigma factor RpoN. Using a combination of RNA-seq, ChIP-seq and molecular biology approaches, we demonstrate that RpoN coordinates the T6SSs of P. aeruginosa by activating the H2-T6SS but repressing the H1- and H3-T6SS. Furthermore, RpoN and Sfa2 control the expression of the H2-T6SS-linked VgrGs and their effector arsenal to enable very effective interbacterial killing. Sfa2 is specific as Sfa3 from the H3-T6SS cannot complement loss of Sfa2. Our study further delineates the regulatory mechanisms that modulate the deployment of an arsenal of T6SS effectors likely enabling P. aeruginosa to adapt to a range of environmental conditions.
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影响因子：
14.9
作者：
Balasubramanian D;Schneper L;Kumari H;Mathee K
通讯作者：
Mathee K
影响因子：
6.7
作者：
Alteri CJ;Himpsl SD;Pickens SR;Lindner JR;Zora JS;Miller JE;Arno PD;Straight SW;Mobley HL
通讯作者：
Mobley HL
DOI：
10.1073/pnas.1917587117
发表时间：
2020-05-12
影响因子：
11.1
作者：
Gebhardt, Michael J.;Kambara, Tracy K.;Dove, Simon L.
通讯作者：
Dove, Simon L.
影响因子：
64.5
作者：
Basler M;Ho BT;Mekalanos JJ
通讯作者：
Mekalanos JJ
影响因子：
2.8
作者：
Burrowes, E;Baysse, C;O'Gara, F
通讯作者：
O'Gara, F