The ancestral stringent response potentiator, DksA has been adapted throughout Salmonella evolution to orchestrate the expression of metabolic, motility, and virulence pathways.
The ancestral stringent response potentiator, DksA has been adapted throughout Salmonella evolution to orchestrate the expression of metabolic, motility, and virulence pathways.
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DOI：
10.1080/19490976.2021.1997294
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发表时间：
2022-01
期刊：
影响因子：
12.2
通讯作者：
Gal-Mor O
中科院分区：
文献类型：
--
作者：
Cohen H;Adani B;Cohen E;Piscon B;Azriel S;Desai P;Bähre H;McClelland M;Rahav G;Gal-Mor O
DksA是一种保守的RNA聚合酶结合蛋白，已知在变形菌属物种（包括许多胃肠道病原体）的严格反应中发挥关键作用。在这里，我们使用的大肠杆菌，沙门氏菌和沙门氏菌肠血清型鼠伤寒沙门氏菌的RNA测序，连同表型比较，研究在沙门氏菌进化过程中DksA调节子的变化。比较RNA测序显示，在非饥饿条件下，DksA控制了25%、15%和20%的E. coli、S. bongori和S.肠道基因，分别表明DksA是一个多效性调节，扩大其作用超越了典型的严格的反应。我们证明，DksA是必需的这三种肠道细菌在基本培养基中的生长，并控制TCA循环，糖酵解，嘧啶生物合成和群体感应的表达。有趣的是，在沙门氏菌进化过程中的多个步骤中，I型菌毛和SPI 1、2、4、5和11内编码的各种毒力基因已在祖先DksA调节子下转录整合。因此，我们表明DksA是必需的宿主细胞入侵由S。鼠伤寒和沙门氏菌。bongori和S.骨髓源性巨噬细胞（BMDM）中的鼠伤寒杆菌。此外，我们证明了DksA对保守的运动趋化性调节子的调节逆转，DksA在E. coli中激活，而在S. bongori和S.肠的。总体而言，这项研究表明，多个水平获得的毒力基因的DksA调节子下的监管同化，并提供了新的见解沙门氏菌的毒力基因调控的演变。
DksA is a conserved RNA polymerase-binding protein known to play a key role in the stringent response of proteobacteria species, including many gastrointestinal pathogens. Here, we used RNA-sequencing of Escherichia coli, Salmonella bongori and Salmonella enterica serovar Typhimurium, together with phenotypic comparison to study changes in the DksA regulon, during Salmonella evolution. Comparative RNA-sequencing showed that under non-starved conditions, DksA controls the expression of 25%, 15%, and 20% of the E. coli, S. bongori, and S. enterica genes, respectively, indicating that DksA is a pleiotropic regulator, expanding its role beyond the canonical stringent response. We demonstrate that DksA is required for the growth of these three enteric bacteria species in minimal medium and controls the expression of the TCA cycle, glycolysis, pyrimidine biosynthesis, and quorum sensing. Interestingly, at multiple steps during Salmonella evolution, the type I fimbriae and various virulence genes encoded within SPIs 1, 2, 4, 5, and 11 have been transcriptionally integrated under the ancestral DksA regulon. Consequently, we show that DksA is necessary for host cells invasion by S. Typhimurium and S. bongori and for intracellular survival of S. Typhimurium in bone marrow-derived macrophages (BMDM). Moreover, we demonstrate regulatory inversion of the conserved motility-chemotaxis regulon by DksA, which acts as a negative regulator in E. coli, but activates this pathway in S. bongori and S. enterica. Overall, this study demonstrates the regulatory assimilation of multiple horizontally acquired virulence genes under the DksA regulon and provides new insights into the evolution of virulence genes regulation in Salmonella spp.
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影响因子：
15.9
作者：
Baumler, AJ
通讯作者：
Baumler, AJ
影响因子：
15.8
作者：
Havelaar AH;Kirk MD;Torgerson PR;Gibb HJ;Hald T;Lake RJ;Praet N;Bellinger DC;de Silva NR;Gargouri N;Speybroeck N;Cawthorne A;Mathers C;Stein C;Angulo FJ;Devleesschauwer B;World Health Organization Foodborne Disease Burden Epidemiology Reference Group
通讯作者：
World Health Organization Foodborne Disease Burden Epidemiology Reference Group
影响因子：
3.2
作者：
Ancona, Veronica;Lee, Jae Hoon;Zhao, Youfu
通讯作者：
Zhao, Youfu
影响因子：
3.6
作者：
Aberg, Anna;Shingler, Victoria;Balsalobre, Carlos
通讯作者：
Balsalobre, Carlos
影响因子：
3.2
作者：
BUCHANAN, K;FALKOW, S;HULL, SI
通讯作者：
HULL, SI