Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, 06536, USA.
Nat Commun. 2024 Nov 29;15(1):10417. doi: 10.1038/s41467-024-54806-w.
Flagella propel pathogens through their environments, yet are expensive to synthesize and are immunogenic. Thus, complex hierarchical regulatory networks control flagellar gene expression. Spirochetes are highly motile bacteria, but peculiarly, the archetypal flagellar regulator σ is absent in the Lyme spirochete Borrelia burgdorferi. Here, we show that gene bb0268 (flgV) in B. burgdorferi, previously and incorrectly annotated to encode the RNA-binding protein Hfq, is instead a structural flagellar component that modulates flagellar assembly. The flgV gene is broadly conserved in the flagellar superoperon alongside σ in many Spirochaetae, Firmicutes and other phyla, with distant homologs in Epsilonproteobacteria. We find that B. burgdorferi FlgV is localized within flagellar basal bodies, and strains lacking flgV produce fewer and shorter flagellar filaments and are defective in cell division and motility. During the enzootic cycle, flgV-deficient B. burgdorferi survive and replicate in Ixodes ticks but are attenuated for infection and dissemination in mice. Our work defines infection timepoints when spirochete motility is most crucial and implicates FlgV as a broadly distributed structural flagellar component that modulates flagellar assembly.
鞭毛推动病原体在其环境中移动，但合成成本高昂，且具有免疫原性。因此，复杂的分层调节网络控制着鞭毛基因的表达。螺旋体是高度能动的细菌，但奇特的是，莱姆螺旋体伯氏疏螺旋体中不存在典型的鞭毛调节因子σ。在这里，我们表明，伯氏疏螺旋体中的 bb0268（flgV）基因，以前被错误注释为编码 RNA 结合蛋白 Hfq，实际上是一个调节鞭毛组装的结构鞭毛成分。该 flgV 基因在许多螺旋体、厚壁菌门和其他门的鞭毛超级操纵子中与 σ广泛保守，在 ε 变形菌中具有遥远的同源物。我们发现，伯氏疏螺旋体 FlgV 定位于鞭毛基体中，flgV 缺失株产生的鞭毛丝更少、更短，细胞分裂和运动功能缺陷。在动物媒介的自然循环中，flgV 缺失的伯氏疏螺旋体在硬蜱中存活和复制，但在感染和传播方面在小鼠中减弱。我们的工作定义了螺旋体运动最关键的感染时间点，并将 FlgV 确定为一种广泛分布的结构鞭毛成分，调节鞭毛组装。
