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Among these, dihydrouridine is a conserved tRNA modification synthesized by the flavin-dependent enzymes DusA, DusB, and DusC, which introduce flexibility at defined uridine positions in the D-loop. While structural and biochemical studies in\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      have clarified dihydrouridine synthase (Dus) enzyme substrate specificities, their functional relevance in other bacteria remains uncharacterized. Here, we present the first functional characterization of the contribution of Dus enzymes to an important urinary tract pathogen,\n                      <jats:italic toggle=\"yes\">Proteus mirabilis<\/jats:italic>\n                      . Mutants were generated in\n                      <jats:italic toggle=\"yes\">dusA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">dusB<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">dusC<\/jats:italic>\n                      in\n                      <jats:italic toggle=\"yes\">P. mirabilis<\/jats:italic>\n                      strain HI4320 for evaluation of virulence-relevant phenotypes. All mutants grew similarly to wild type under multiple conditions, although loss of\n                      <jats:italic toggle=\"yes\">dusB<\/jats:italic>\n                      caused a competitive fitness defect. Disruption of\n                      <jats:italic toggle=\"yes\">dusB<\/jats:italic>\n                      also resulted in increased biofilm biomass, impaired swimming motility, enhanced outer membrane permeability, and increased susceptibility to detergents and antibiotics, while disruption of\n                      <jats:italic toggle=\"yes\">dusA<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">dusC<\/jats:italic>\n                      only impacted biofilm formation and susceptibility to detergents. In a murine model of catheter-associated urinary tract infection,\n                      <jats:italic toggle=\"yes\">dusB<\/jats:italic>\n                      was critical for fitness in all organs during co-challenge against wild type as well as overall colonization during independent challenge. In contrast,\n                      <jats:italic toggle=\"yes\">dusC<\/jats:italic>\n                      did not contribute to fitness, and\n                      <jats:italic toggle=\"yes\">dusA<\/jats:italic>\n                      showed a modest, compartment-specific contribution to fitness, as the\n                      <jats:italic toggle=\"yes\">dusA::Kan<\/jats:italic>\n                      mutant was outcompeted in the bladder. Together, these findings identify DusB as a key regulator of motility, membrane integrity, and host fitness in\n                      <jats:italic toggle=\"yes\">P. mirabilis<\/jats:italic>\n                      , linking Dus enzymes to virulence-associated phenotypes, potentially through effects on RNA modification and\/or additional protein functions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00722-25","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:09:18Z","timestamp":1777280958000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Contribution of three tRNA modification enzymes to\n                    <i>Proteus mirabilis<\/i>\n                    fitness and catheter-associated urinary tract infection"],"prefix":"10.1128","volume":"94","author":[{"given":"Vitus","family":"Brix","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C.","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Learman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee L.","family":"Brauer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-2759","authenticated-orcid":true,"given":"Chelsie E.","family":"Armbruster","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.2c00307"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2017.06.011"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01743-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1294"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.10.009"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-153"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1500161112"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309113019489"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607512113"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa548"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1276"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","unstructured":"Schultz SK Hossain N Barnes L Koutmou KS Kothe U. 2025. 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