Wang Yaqi, Cao Wei, Merritt Justin, Xie Zhoujie, Liu Hao
MOE Key Laboratory of Industrial Fermentation Microbiology, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China.
Department of Restorative Dentistry, Oregon Health & Science University, Portland, OR, United States.
Front Genet. 2021 Apr 27;12:659220. doi: 10.3389/fgene.2021.659220. eCollection 2021.
FtsH belongs to the AAA+ ATP-dependent family of proteases, which participate in diverse cellular processes and are ubiquitous among bacteria, chloroplasts, and mitochondria. FtsH is poorly characterized in most organisms, especially compared to other major housekeeping proteases. In the current study, we examined the source of FtsH essentiality in the human oral microbiome species , one of the primary etiological agents of dental caries. By creating a conditionally lethal mutant, we were able to identify a secondary suppressor missense mutation in the gene, encoding the response regulator of the essential VicRK two-component system (TCS). Transcriptomic analysis of the (G195R) mutant revealed significantly reduced expression of 46 genes, many of which were located within the genomic island Tnsmu2, which harbors the mutanobactin biosynthetic gene cluster. In agreement with the transcriptomic data, deletion of the mutanobactin biosynthetic gene cluster suppressed essentiality in . We also explored the role of FtsH in physiology and demonstrated its critical role in stress tolerance, especially acid stress. The presented results reveal the first insights within for the pleiotropic regulatory function of this poorly understood global regulator.
FtsH属于AAA+依赖ATP的蛋白酶家族，该家族参与多种细胞过程，在细菌、叶绿体和线粒体中普遍存在。在大多数生物体中，FtsH的特征尚不明确，尤其是与其他主要的管家蛋白酶相比。在本研究中，我们研究了人类口腔微生物物种中FtsH必需性的来源，该物种是龋齿的主要病原体之一。通过创建一个条件致死突变体，我们能够在编码必需的VicRK双组分系统（TCS）应答调节因子的基因中鉴定出一个二级抑制错义突变。对（G195R）突变体的转录组分析显示，46个基因的表达显著降低，其中许多基因位于基因组岛Tnsmu2内，该岛含有变链菌素生物合成基因簇。与转录组数据一致，变链菌素生物合成基因簇的缺失抑制了在中的必需性。我们还探讨了FtsH在生理中的作用，并证明了其在应激耐受性，尤其是酸应激中的关键作用。所呈现的结果揭示了对这种了解甚少的全局调节因子的多效性调节功能的首次见解。
