A virulence activator of a surface attachment protein in Burkholderia pseudomallei acts as a global regulator of other membrane-associated virulence factors.
A virulence activator of a surface attachment protein in Burkholderia pseudomallei acts as a global regulator of other membrane-associated virulence factors.
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DOI：
10.3389/fmicb.2022.1063287
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发表时间：
2022
影响因子：
5.2
通讯作者：
Hoang, Tung T.
中科院分区：
文献类型：
--
作者：
Sun, Zhenxin;Heacock-Kang, Yun;McMillan, Ian A.;Cabanas, Darlene;Zarzycki-Siek, Jan;Hoang, Tung T.
关键词：
类鼻疽伯克霍尔德氏菌（Bp）是一种兼性细胞内病原体，可附着并侵入多种细胞类型，引起高度致命的类鼻疽病。我们以前确定BP1026B_I0091作为一个表面附着蛋白（Sap1）和一个重要的毒力因子，有助于在体外和体内的Bp发病机制。sap 1的表达在Bp细胞内生命周期的不同阶段由未鉴定的调节剂调节。在这里，我们确定了SapR（BP1026B_II1046）作为一个转录调节因子，激活sap1，使用高通量转座子诱变筛选结合Tn-Seq。与Δ sap1突变体的表型一致，Δ sapR激活剂突变体表现出Bp与宿主细胞的附着显著减少，导致随后的细胞内复制减少。RNA-Seq分析进一步揭示了SapR调节sap1。通过qRT-PCR定量证实了SapR对sap1的调控，这也验证了RNA-Seq数据。SapR响应于不同的环境而全面调节与细菌膜相关的基因，并且由SapR调节的一些基因是Bp细胞内感染所需的毒力因子（例如，III型和VI型分泌系统）。这项研究已经确定了复杂的SapR调控网络及其作为必需的Sap1附着因子激活剂的重要性。
Burkholderia pseudomallei (Bp), causing a highly fatal disease called melioidosis, is a facultative intracellular pathogen that attaches and invades a variety of cell types. We previously identified BP1026B_I0091 as a surface attachment protein (Sap1) and an essential virulence factor, contributing to Bp pathogenesis in vitro and in vivo. The expression of sap1 is regulated at different stages of Bp intracellular lifecycle by unidentified regulator(s). Here, we identified SapR (BP1026B_II1046) as a transcriptional regulator that activates sap1, using a high-throughput transposon mutagenesis screen in combination with Tn-Seq. Consistent with phenotypes of the Δsap1 mutant, the ΔsapR activator mutant exhibited a significant reduction in Bp attachment to the host cell, leading to subsequent decreased intracellular replication. RNA-Seq analysis further revealed that SapR regulates sap1. The regulation of sap1 by SapR was confirmed quantitatively by qRT-PCR, which also validated the RNA-Seq data. SapR globally regulates genes associated with the bacterial membrane in response to diverse environments, and some of the genes regulated by SapR are virulence factors that are required for Bp intracellular infection (e.g., type III and type VI secretion systems). This study has identified the complex SapR regulatory network and its importance as an activator of an essential Sap1 attachment factor.
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影响因子：
2.7
作者：
Kang WT;Vellasamy KM;Rajamani L;Beuerman RW;Vadivelu J
通讯作者：
Vadivelu J
影响因子：
6.7
作者：
Chaput C;Ecobichon C;Cayet N;Girardin SE;Werts C;Guadagnini S;Prévost MC;Mengin-Lecreulx D;Labigne A;Boneca IG
通讯作者：
Boneca IG
影响因子：
48
作者：
Choi, KH;Gaynor, JB;Schweizer, HP
通讯作者：
Schweizer, HP
影响因子：
3.1
作者：
Chen, Yahua;Wong, Jocelyn;Gan, Yunn-Hwen
通讯作者：
Gan, Yunn-Hwen
影响因子：
4.2
作者：
Balder, Rachel;Lipski, Serena;Lafontaine, Eric R.
通讯作者：
Lafontaine, Eric R.