{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:04:30Z","timestamp":1786460670885,"version":"build-2736575974"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI165582"],"award-info":[{"award-number":["R01AI165582"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Cytolethal distending toxin (CDT) is a virulence factor produced by several gram-negative bacteria, including\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      , the most prevalent etiological agent of urinary tract infections (UTIs). CDT causes DNA damage to eukaryotic cells, leading to the impairment of host defenses by disrupting epithelial barriers, suppressing acquired immunity, and promoting pro-inflammatory responses.\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      strains encoding CDT have been previously identified in samples from UTI patients; however, the specific function of CDT in the development of UTI remains undefined. In this study, we used a mouse model of ascending UTI to determine the role of CDT during infection. An\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      mutant strain lacking the\n                      <jats:italic toggle=\"yes\">cdtABC<\/jats:italic>\n                      locus was generated and combined with wild-type bacteria to co-infect mice via transurethral inoculation. At 1 day post-inoculation, competitive indices demonstrated a significant disadvantage for the\n                      <jats:italic toggle=\"yes\">cdt<\/jats:italic>\n                      mutant in urine, bladder, and kidneys. Single-strain infections were also performed as a further assessment of CDT impact, demonstrating that the\n                      <jats:italic toggle=\"yes\">cdt<\/jats:italic>\n                      mutant had reduced kidney colonization, indicative of CDT contributions to pyelonephritis. Histopathological analysis of the urinary bladder and kidney tissues from mice infected with CDT-encoding\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      demonstrated higher levels of inflammation and tissue damage within the kidneys at both 1 and 7 days post-inoculation and in the bladder after 7 days when compared to mice infected with\n                      <jats:italic toggle=\"yes\">cdt<\/jats:italic>\n                      mutant bacteria. Collectively, these findings identify a role for CDT in UTI pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00103-26","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:03:57Z","timestamp":1783951437000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Cytolethal distending toxin enhances\n                    <i>Escherichia coli<\/i>\n                    urinary tract infection"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5266-391X","authenticated-orcid":true,"given":"Santosh","family":"Paudel","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan, Michigan Medicine","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin E.","family":"Curtis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit for Laboratory Animal Medicine Pathology Core, University of Michigan, Michigan Medicine","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siena","family":"Stefa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan, Michigan Medicine","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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