Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, Serbia.
Faculty of Biology, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia.
Int J Mol Sci. 2022 Jul 26;23(15):8232. doi: 10.3390/ijms23158232.
Signal transduction systems are the key players of bacterial adaptation and survival. The orthodox two-component signal transduction systems perceive diverse environmental stimuli and their regulatory response leads to cellular changes. Although rarely described, the unorthodox three-component systems are also implemented in the regulation of major bacterial behavior such as the virulence of clinically relevant pathogen . Previously, we described a novel three-component system in WCS358 (RclSAR) where the sensor kinase RclS stimulates the transcription in stationary growth phase. In this study, using knock-out mutant, we identified RclSAR regulon in WCS358. The RNA sequencing revealed that activity of RclSAR signal transduction system is growth phase dependent with more pronounced regulatory potential in early stages of growth. Transcriptional analysis emphasized the role of RclSAR in global regulation and indicated the involvement of this system in regulation of diverse cellular activities such as RNA binding and metabolic and biocontrol processes. Importantly, phenotypic comparison of WCS358 wild type and Δ mutant showed that RclS sensor kinase contributes to modulation of antibiotic resistance, production of AHLs and siderophore as well as host cell adherence and cytotoxicity. Finally, we proposed the improved model of interplay between RclSAR, RpoS and LasIR regulatory systems in WCS358.
信号转导系统是细菌适应和生存的关键因素。传统的双组分信号转导系统感知多种环境刺激,其调节反应导致细胞变化。尽管很少有描述,但非传统的三组分系统也被用于调节主要的细菌行为,如临床相关病原体的毒力。之前,我们在 WCS358(RclSAR)中描述了一个新的三组分系统,其中传感器激酶 RclS 刺激了在静止生长阶段的转录。在这项研究中,我们使用敲除突变体,确定了 WCS358 中 RclSAR 调控组。RNA 测序表明,RclSAR 信号转导系统的活性与生长阶段有关,在生长的早期阶段具有更明显的调节潜力。转录分析强调了 RclSAR 在全局调节中的作用,并表明该系统参与了调节多种细胞活动,如 RNA 结合以及代谢和生物防治过程。重要的是,WCS358 野生型和Δ突变体的表型比较表明,RclS 传感器激酶有助于调节抗生素抗性、AHL 和铁载体的产生以及宿主细胞粘附和细胞毒性。最后,我们提出了 RclSAR、RpoS 和 LasIR 调节系统在 WCS358 中相互作用的改进模型。