PDF(Pubmed)
Abstract：
tRNA modifications play a crucial role in ensuring accurate codon recognition and optimizing translation levels. While the significance of these modifications in eukaryotic cells for maintaining cellular homeostasis and physiological functions is well-established, their physiological roles in bacterial cells, particularly in pathogenesis, remain relatively unexplored. The TusDCB protein complex, conserved in γ-proteobacteria like Escherichia coli, is involved in sulfur modification of specific tRNAs. This study focused on the role of TusDCB in the virulence of uropathogenic E. coli (UPEC), a bacterium causing urinary tract infections. The findings indicate that TusDCB is essential for optimal production of UPEC\'s virulence factors, including type 1 fimbriae and flagellum, impacting the bacterium\'s ability to aggregate in bladder epithelial cells. Deletion of tusDCB resulted in decreased virulence against urinary tract infection mice. Moreover, mutant TusDCB lacking sulfur transfer activity and tusE- and mnmA mutants revealed the indispensability of TusDCB\'s sulfur transfer activity for UPEC pathogenicity. The study extends its relevance to highly pathogenic, multidrug-resistant strains, where tusDCB deletion reduced virulence-associated bacterial aggregation. These insights not only deepen our understanding of the interplay between tRNA sulfur modification and bacterial pathogenesis but also highlight TusDCB as a potential therapeutic target against UPEC strains resistant to conventional antimicrobial agents.
摘要：
tRNA修饰在确保准确的密码子识别和优化翻译水平中起着至关重要的作用。虽然这些修饰在真核细胞中对维持细胞稳态和生理功能的重要性已经确立,它们在细菌细胞中的生理作用，特别是在发病机制中，相对未被探索。TusDCB蛋白复合物，在像大肠杆菌一样的γ-蛋白细菌中保守，参与特定tRNA的硫修饰。本研究主要探讨TusDCB在尿路致病性大肠杆菌(UPEC)毒力中的作用,引起尿路感染的细菌。研究结果表明，TusDCB对于UPEC毒力因子的最佳生产至关重要，包括1型菌毛和鞭毛,影响细菌在膀胱上皮细胞中聚集的能力。tusDCB的缺失导致对尿路感染小鼠的毒力降低。此外，缺乏硫转移活性的突变体TusDCB和tus-和mnmA突变体揭示了TusDCB的硫转移活性对UPEC致病性的不可或缺性。该研究将其相关性扩展到高致病性，多重耐药菌株，其中tusDCB缺失减少了毒力相关的细菌聚集。这些见解不仅加深了我们对tRNA硫修饰与细菌发病机理之间相互作用的理解，而且还强调了TusDCB作为对常规抗微生物剂耐药的UPEC菌株的潜在治疗靶标。
