Beijing Laboratory for Food Quality and Safety, College of Food Science & Nutritional Engineering, China Agricultural Universitygrid.22935.3f, Beijing, People's Republic of China.
Laboratory of Nutrient Resources and Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Science, Tianjin, People's Republic of China.
Microbiol Spectr. 2022 Dec 21;10(6):e0205522. doi: 10.1128/spectrum.02055-22. Epub 2022 Nov 21.
Stringent response plays an important role in the response of pathogens to rapid environmental changes. It has been shown that synergistic and antagonistic actions exist between the signaling molecules (p)ppGpp and DksA in several foodborne pathogens; however, the biological function of these molecules and their interactions in are still unclear. This study systematically investigated the role of stringent response in Yersinia enterocolitica, a typical foodborne pathogen, by deleting the (p)ppGpp and DksA biosynthesis genes. (p)ppGpp and DksA copositively regulated most phenotypes, such as motility, antibiotic resistance, and tolerance to oxidative stress, whereas they exhibited independent and/or divergent roles in the growth and biofilm synthesis of Y. enterocolitica. Gene expression analysis revealed that (p)ppGpp- and DksA-deficiency reduced the transcription of flagellar synthesis genes ( and ) and biofilm synthesis genes ( and ), which could potentially contribute to changes in motility and biofilm formation. These results indicate that stringent response regulators (p)ppGpp and DksA have a synergistic role and independent or even completely opposite biological functions in regulating genes and phenotypes of Y. enterocolitica. Our findings revealed the biofunctional relationships between (p)ppGpp and DksA and the underlying molecular mechanisms in the regulation of the pathogenic phenotype of Y. enterocolitica. The synergetic actions between the stringent response signaling molecules, (p)ppGpp and DksA, have been widely reported. However, recent transcriptomic and phenotypic studies have suggested that independent or even opposite actions exist between them. In this study, we demonstrated that the knockout of (p)ppGpp and DksA affects the polymorphic phenotype of Yersinia enterocolitica. Although most of the tested phenotypes, such as motility, antibiotic resistance, and tolerance to oxidative stress, were copositively regulated by (p)ppGpp and DksA, it also showed inconsistencies in biofilm formation ability as well as some independent phenotypes. This study deepens our understanding of the strategies of foodborne pathogens to survive in complex environments, so as to provide theoretical basis for the control and treatment of these microorganisms.
严格响应在病原体对快速环境变化的响应中起着重要作用。已经表明，信号分子（p）ppGpp 和 DksA 之间在几种食源性病原体中存在协同和拮抗作用；然而，这些分子的生物学功能及其相互作用在 中仍然不清楚。本研究通过删除（p）ppGpp 和 DksA 生物合成基因，系统地研究了严格响应在典型食源性病原体 中的作用。（p）ppGpp 和 DksA 共同调节大多数表型，如运动性、抗生素抗性和对氧化应激的耐受性，而它们在 中对 Y. enterocolitica 的生长和生物膜合成具有独立和/或不同的作用。基因表达分析表明，（p）ppGpp 和 DksA 缺陷降低了鞭毛合成基因（和）和生物膜合成基因（和）的转录，这可能导致运动性和生物膜形成的变化。这些结果表明，严格响应调节剂（p）ppGpp 和 DksA 在调节 Y. enterocolitica 的基因和表型方面具有协同作用和独立的甚至完全相反的生物学功能。我们的研究结果揭示了（p）ppGpp 和 DksA 之间的生物功能关系以及严格响应信号分子在调节 Y. enterocolitica 致病表型中的潜在分子机制。（p）ppGpp 和 DksA 之间的严格响应信号分子的协同作用已被广泛报道。然而，最近的转录组学和表型研究表明，它们之间存在独立的甚至相反的作用。在本研究中，我们证明了（p）ppGpp 和 DksA 的敲除影响了 Yersinia enterocolitica 的多态表型。尽管大多数测试的表型，如运动性、抗生素抗性和对氧化应激的耐受性，都被（p）ppGpp 和 DksA 共同调节，但在生物膜形成能力以及一些独立表型方面也存在不一致性。本研究加深了我们对食源性病原体在复杂环境中生存策略的理解，为这些微生物的控制和治疗提供了理论依据。
