Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation in Vibrio cholerae.
Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation in Vibrio cholerae.
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DOI：
10.1016/j.jbc.2023.105147
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发表时间：
2023-09
影响因子：
4.8
通讯作者：
Capdevila, Daiana A.
中科院分区：
文献类型：
--
作者：
Diez, Cristian M. Pis;Antelo, Giuliano T.;Dalia, Triana N.;Dalia, Ankur B.;Giedroc, David P.;Capdevila, Daiana A.
脊椎动物宿主的免疫系统和常驻的共生细菌部署了一系列高度反应性的小分子，为微生物病原体的感染提供了屏障。肠道病原体，如霍乱弧菌，通过调节对定植至关重要的外毒素的表达来感知和响应这些压力源。在这里，我们采用基于质谱的谱分析、代谢组学、表达分析和生物物理方法来显示霍乱弧菌溶血素基因hlyA的转录激活是由细胞内硫的硫-硫键形式调节的，称为活性硫物种（RSS）。我们首先提出了一个全面的序列相似性网络分析砷抑制子转录调控子超家族，其中RSS和过氧化氢传感器分离成不同的序列簇。我们发现，霍乱弧菌中hlyA的转录激活剂HlyU属于rss感应簇，并且很容易与有机过硫化物反应，在谷胱甘肽二硫化物或过氧化氢处理后没有反应性或DNA解离。令人惊讶的是，在霍乱弧菌细胞培养中，硫化物和过氧化物处理均下调hlyA依赖的转录激活。然而，RSS代谢物分析显示，硫化物和过氧化物处理都能在相似程度上提高内源性无机硫化物和二硫化物水平，从而解释了这种串音，并证实了霍乱弧菌在细胞内RSS的特异性反应中减弱了hyu介导的hlyA激活。这些发现提供了新的证据，表明肠道病原体可能利用rss感知作为一种进化适应，使它们能够通过调节外毒素的表达来克服肠道炎症反应。
The vertebrate host's immune system and resident commensal bacteria deploy a range of highly reactive small molecules that provide a barrier against infections by microbial pathogens. Gut pathogens, such as Vibrio cholerae, sense and respond to these stressors by modulating the expression of exotoxins that are crucial for colonization. Here, we employ mass spectrometry–based profiling, metabolomics, expression assays, and biophysical approaches to show that transcriptional activation of the hemolysin gene hlyA in V. cholerae is regulated by intracellular forms of sulfur with sulfur–sulfur bonds, termed reactive sulfur species (RSS). We first present a comprehensive sequence similarity network analysis of the arsenic repressor superfamily of transcriptional regulators, where RSS and hydrogen peroxide sensors segregate into distinct clusters of sequences. We show that HlyU, transcriptional activator of hlyA in V. cholerae, belongs to the RSS-sensing cluster and readily reacts with organic persulfides, showing no reactivity or DNA dissociation following treatment with glutathione disulfide or hydrogen peroxide. Surprisingly, in V. cholerae cell cultures, both sulfide and peroxide treatment downregulate HlyU-dependent transcriptional activation of hlyA. However, RSS metabolite profiling shows that both sulfide and peroxide treatment raise the endogenous inorganic sulfide and disulfide levels to a similar extent, accounting for this crosstalk, and confirming that V. cholerae attenuates HlyU-mediated activation of hlyA in a specific response to intracellular RSS. These findings provide new evidence that gut pathogens may harness RSS-sensing as an evolutionary adaptation that allows them to overcome the gut inflammatory response by modulating the expression of exotoxins.
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DOI：
10.3390/antiox11122359
发表时间：
2022-11-28
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
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影响因子：
11.4
作者：
Akiyama, Masahiro;Unoki, Takamitsu;Aoki, Hanako;Nishimura, Akiyuki;Shinkai, Yasuhiro;Warabi, Eiji;Nishiyama, Kazuhiro;Furumoto, Yuka;Anzai, Naohiko;Akaike, Takaaki;Nishida, Motohiro;Kumagai, Yoshito
通讯作者：
Kumagai, Yoshito
影响因子：
6.4
作者：
Capdevila DA;Edmonds KA;Giedroc DP
通讯作者：
Giedroc DP
转录调节剂中硫化物感应特异性的结构基础。
影响因子：
14.8
作者：
Capdevila DA;Walsh BJC;Zhang Y;Dietrich C;Gonzalez-Gutierrez G;Giedroc DP
通讯作者：
Giedroc DP
DOI：
10.1016/j.scitotenv.2020.142393
发表时间：
2021-02-01
期刊：
The Science of the total environment
影响因子：
--
作者：
An L;Luo X;Wu M;Feng L;Shi K;Wang G;Rosen BP;Li M
通讯作者：
Li M