{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:35:12Z","timestamp":1791304512967,"version":"4.3.1"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"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":["R21AI146375-01A1"],"award-info":[{"award-number":["R21AI146375-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01AI116453-06"],"award-info":[{"award-number":["2R01AI116453-06"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,6,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Brucellosis, one of the most prevalent zoonotic diseases worldwide, often results in osteoarticular complications including large joint and axial arthritis mimicking spondyloarthritis. To model this chronic manifestation, we infected autoimmunity-prone SKG mice containing a mutation in the T cell adaptor ZAP-70 with\n                      <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                      species.\n                      <jats:italic toggle=\"yes\">B. melitensis<\/jats:italic>\n                      infection resulted in a fully penetrant, readily scoreable disease involving large joint wrist and foot arthritis, peri-ocular inflammation, and less frequent scaly paw rash. Infection with\n                      <jats:italic toggle=\"yes\">B. abortus<\/jats:italic>\n                      resulted in similar manifestations, although with delayed arthritis onset, and\n                      <jats:italic toggle=\"yes\">B. neotomae<\/jats:italic>\n                      revealed sex differences, with a more severe disease in females. Heat-killed\n                      <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                      did not induce arthritis, evincing a requirement for viable infection. Across species, splenic CFU correlated well with final clinical score at 12 weeks (\u03c1 = 0.79 and\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). Moreover, viable\n                      <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                      was recovered from the paws at 12 weeks, consistent with persistent articular infection. Mice infected with a\n                      <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">tcpB<\/jats:italic>\n                      mutant lacking a Type IV secretion system-dependent mediator displayed an intermediate phenotype without significant differences in splenic CFU. Thus, the degree of arthritis did not strictly correlate with the degree of systemic infection, but it suggested an additional reactive component. Together, these data suggest that\n                      <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                      -induced spondyloarthritis reflects both persistent colonization and excess host reactivity. Moreover, the sensitivity of the SKG model to different species and mutants will provide new opportunities for dissecting correlates of\n                      <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                      virulence and host immunity.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Brucellosis, a bacterial infection acquired from herd animals, remains one of the most common zoonotic diseases worldwide. Chronic infection often results in spondyloarthritis-like complications. Investigation into pathogenesis has been limited by the lack of overt disease in standard laboratory mice. We addressed this issue using spondyloarthritis-susceptible SKG mice. Upon infection with\n                        <jats:italic toggle=\"yes\">B. melitensis<\/jats:italic>\n                        , SKG mice develop robust, fully penetrant large joint arthritis. Arthritis development required viable bacteria, and live\n                        <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                        persisted in paw tissue out to 12 weeks. Disease onset, severity, and manifestations varied upon infection with different\n                        <jats:italic toggle=\"yes\">Brucella<\/jats:italic>\n                        species and mutants, suggesting an additional immune reactive component. Together, these results suggest that this new model will be very useful to the scientific community for determining correlates of bacterial virulence leading to clinical disease.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00542-25","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T09:00:21Z","timestamp":1747213221000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Persistent articular infection and host reactive response contribute to\n                    <i>Brucella<\/i>\n                    -induced spondyloarthritis in SKG mice"],"prefix":"10.1128","volume":"16","author":[{"given":"Jerome S.","family":"Harms","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01e4byj08","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Pediatrics and Medical Microbiology 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