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CqsA/LuxS-HapR 群体感应电路调节. 中的 VI 型分泌系统 VflT6SS2

CqsA/LuxS-HapR Quorum sensing circuit modulates type VI secretion system VflT6SS2 in .

机构信息

State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, People's Republic of China.

出版信息

Emerg Microbes Infect. 2021 Dec;10(1):589-601. doi: 10.1080/22221751.2021.1902244.

DOI:10.1080/22221751.2021.1902244
PMID:33689580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8018390/
Abstract

is an emerging enteric pathogen of increasing public health threat. Two quorum sensing (QS) systems, VfqI-VfqR and CqsA/LuxS-HapR, and two type VI secretion systems (T6SSs), VflT6SS1 and VflT6SS2, have been identified in . Whether there exists any correlation between the two systems is unclear. In this study, we found that CqsA/LuxS-HapR circuit regulator LuxO represses while HapR activates VflT6SS2. The effect of LuxO is more pronounced at low cell density and is HapR-dependent. Deletion of abolished Hcp expression and alleviated antibacterial virulence. However, these effects were rescued by HapR-expressing plasmid. Reporter fusion analyses showed that HapR is required for the promoter activities of VflT6SS2. Sequence inspection of the major cluster promoter revealed two potential Motif 1 HapR binding sites, and their bindings to HapR were confirmed by both electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay. Meanwhile, two single Motif 2 sites were identified in 2_a (A) and 2_b (B) promoter regions of the orphan cluster which are less conserved and displayed lower affinities to HapR. Together, our study demonstrated that CqsA/LuxS-HapR QS manipulate VflT6SS2 in , and this finding will enhance our understanding of possible crosstalk between T6SS and QS in microbes.

摘要

是一种新兴的肠道病原体,对公共健康构成越来越大的威胁。已经鉴定出两种群体感应(QS)系统,VfqI-VfqR 和 CqsA/LuxS-HapR,以及两种类型的 VI 型分泌系统(T6SSs),VflT6SS1 和 VflT6SS2。两种系统之间是否存在任何相关性尚不清楚。在本研究中,我们发现 CqsA/LuxS-HapR 电路调节 LuxO 抑制而 HapR 激活 VflT6SS2。在低细胞密度下,LuxO 的作用更为明显,且依赖于 HapR。缺失 会导致 Hcp 表达减少并减轻抗菌毒力。然而,这些效应可以通过表达 HapR 的质粒来挽救。报告基因融合分析表明,HapR 是 VflT6SS2 启动子活性所必需的。主要簇启动子的序列检查显示了两个潜在的 Motif 1 HapR 结合位点,并且通过电泳迁移率变动分析(EMSA)和 DNase I 足迹分析证实了它们与 HapR 的结合。同时,在孤儿簇的 2_a(A)和 2_b(B)启动子区域中鉴定出两个单 Motif 2 位点,这些位点的保守性较低,与 HapR 的亲和力较低。总之,我们的研究表明,CqsA/LuxS-HapR QS 在 中操纵 VflT6SS2,这一发现将增强我们对微生物中 T6SS 和 QS 之间可能发生的串扰的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/5f249c5ac879/TEMI_A_1902244_F0007_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/7170f1dd67de/TEMI_A_1902244_F0001_OB.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/6379b47a160f/TEMI_A_1902244_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/ed6c85c6bf3e/TEMI_A_1902244_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/5c6fe956778e/TEMI_A_1902244_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/5f249c5ac879/TEMI_A_1902244_F0007_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/7170f1dd67de/TEMI_A_1902244_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/6526bbb0eef9/TEMI_A_1902244_F0002_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/f7788dcf971a/TEMI_A_1902244_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/6379b47a160f/TEMI_A_1902244_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/ed6c85c6bf3e/TEMI_A_1902244_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/5c6fe956778e/TEMI_A_1902244_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d47/8018390/5f249c5ac879/TEMI_A_1902244_F0007_OB.jpg

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