TusDCB, a sulfur transferase complex involved in tRNA modification, contributes to UPEC pathogenicity

• Published in: Scientific reports Vol. 14; no. 1; p. 8978
• Main Authors: Sato, Yumika, Takita, Ayako, Suzue, Kazutomo, Hashimoto, Yusuke, Hiramoto, Suguru, Murakami, Masami, Tomita, Haruyoshi, Hirakawa, Hidetada
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 18.04.2024; Nature Portfolio
• Subjects: Aggregation; Animals; Antimicrobial agents; Bacteria; Bacterial pathogenesis; Biofilm; Bladder; Clonal deletion; Drug resistance; E coli; Epithelial cells; Escherichia coli; Escherichia coli Infections - microbiology; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Flagella; Homeostasis; Mice; Multidrug resistance; Mutants; Pathogenesis; Pathogenicity; Pathogens; Physiological functions; Physiology; Pili; Strains (organisms); Sulfur; Sulphur; Therapeutic targets; Transfer RNA; Transferases - metabolism; tRNA; tRNA Ala; tRNA modification; Urinary tract; Urinary tract infection (UTI); Urinary Tract Infections - microbiology; Urogenital system; Uropathogenic Escherichia coli; Virulence; Virulence - genetics; Virulence factors; Virulence Factors - genetics; Biofilm; Bacterial pathogenesis; Drug resistance; tRNA modification; Virulence; Urinary tract infection (UTI)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-59614-2

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.