{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:44:45Z","timestamp":1785415485797,"version":"3.56.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["5030-32000-236-000-D"],"award-info":[{"award-number":["5030-32000-236-000-D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Bovine respiratory disease complex (BRDC) is a multifactorial syndrome that involves complex interactions between environment, bacterial\/viral pathogens, and the host.\n                      <jats:italic toggle=\"yes\">Mannheimia haemolytica<\/jats:italic>\n                      is the most significant bacterial pathogen associated with BRDC. This study investigated the virulence of a\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      serotype 1 capsular-deficient (\u0394\n                      <jats:italic toggle=\"yes\">cap<\/jats:italic>\n                      ) mutant and a\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      lipopolysaccharide (LPS)-sialylation-deficient (\u0394\n                      <jats:italic toggle=\"yes\">neuA<\/jats:italic>\n                      , cytidine monophosphate-sialic acid synthetase) mutant in a calf lung challenge model. Twelve colostrum-deprived calves were divided into three groups (four calves per group) and intratracheally administered inoculum of\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      wild-type (WT),\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">cap<\/jats:italic>\n                      , or\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">neuA<\/jats:italic>\n                      strains (~5 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      CFU per animal). Animals were observed for signs of pneumonia and were humanely euthanized 2 to 3 days post-bacterial challenge. Lungs were examined for gross pulmonary lesions, histopathological changes, and bacterial culture. Calves administered WT\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      exhibited severe lung lesions characterized by extensive consolidation and hemorrhage. In contrast, calves administered\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">cap<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">neuA<\/jats:italic>\n                      mutants displayed significantly reduced lung lesions (\n                      <jats:italic toggle=\"yes\">P &lt;<\/jats:italic>\n                      0.05). The most severely affected lung lobes were the right cranial and right middle lobes, with ~50% consolidation. The WT group exhibited significantly higher lung tissue bacterial loads than either of the groups receiving the mutant strains (\n                      <jats:italic toggle=\"yes\">P &lt;<\/jats:italic>\n                      0.05). The reduced clinical signs, pneumonic lung lesions, and bacterial recovery in the lungs of the calves challenged with either the \u0394\n                      <jats:italic toggle=\"yes\">cap<\/jats:italic>\n                      or the \u0394\n                      <jats:italic toggle=\"yes\">neuA M. haemolytica<\/jats:italic>\n                      mutant strains indicated that these mutations were significantly less virulent than the parent strain.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        While\n                        <jats:italic toggle=\"yes\">Mannheimia haemolytica<\/jats:italic>\n                        leukotoxin is well recognized as a major virulence factor, the roles of other possible virulence factors, such as capsule and sialic acid (sialylation of LPS) in\n                        <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                        , have not been investigated in animal models. This study revealed that the abolishment of capsule (\u0394\n                        <jats:italic toggle=\"yes\">cap<\/jats:italic>\n                        ) or LPS sialylation (\u0394\n                        <jats:italic toggle=\"yes\">neuA<\/jats:italic>\n                        ) significantly reduced the virulence of each mutant in calf lung challenges. These results demonstrate that both\n                        <jats:italic toggle=\"yes\">M. haemolytica<\/jats:italic>\n                        capsule and sialylated LPS are important virulence factors that play a key role in the evasion of host defenses.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00283-25","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T09:02:42Z","timestamp":1745398962000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Mannheimia haemolytica<\/i>\n                    isogenic capsular and LPS-sialylation gene deletion mutants are attenuated in a calf lung challenge model"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6773-8304","authenticated-orcid":true,"given":"Harish","family":"Menghwar","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02d2m2044","id-type":"ROR","asserted-by":"publisher"}],"name":"Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, USA Department of Agriculture","place":["Ames, USA"]},{"id":[{"id":"https:\/\/ror.org\/040vxhp34","id-type":"ROR","asserted-by":"publisher"}],"name":"Oak Ridge Institute for Science and Education (ORISE), ARS Research Participation Program","place":["Oak Ridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred M.","family":"Tatum","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02d2m2044","id-type":"ROR","asserted-by":"publisher"}],"name":"Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural 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