{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:35:08Z","timestamp":1767706508010},"reference-count":41,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Mannheimia haemolytica<\/jats:named-content>\n            causes pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-gene\n            <jats:italic>lktCABD<\/jats:italic>\n            operon:\n            <jats:italic>lkt<\/jats:italic>\n            A encodes the structural protoxin, and\n            <jats:italic>lktC<\/jats:italic>\n            encodes a\n            <jats:italic>trans<\/jats:italic>\n            -acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by\n            <jats:italic>lktB<\/jats:italic>\n            and\n            <jats:italic>lktD<\/jats:italic>\n            . It has been reported that LktC-mediated acylation is necessary for the biological effects of the toxin. However, an LktC mutant that we developed previously was only partially attenuated in its virulence for cattle. The objective of this study was to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We performed this study in bighorn sheep (\n            <jats:named-content content-type=\"genus-species\">Ovis canadensis<\/jats:named-content>\n            ) (BHS), since they are highly susceptible to\n            <jats:named-content content-type=\"genus-species\">M. haemolytica<\/jats:named-content>\n            infection. The LktC mutant caused fatal pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the mutant was cytotoxic to BHS PMNs in an\n            <jats:italic>in vitro<\/jats:italic>\n            cytotoxicity assay. Flow cytometric analysis of mutant Lkt-treated PMNs revealed the induction of necrosis. Scanning electron microscopic analysis revealed the presence of pores and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that the mutant secreted an unacylated Lkt. Taken together, these results suggest that acylation is not necessary for the cytotoxic activity of\n            <jats:named-content content-type=\"genus-species\">M. haemolytica<\/jats:named-content>\n            Lkt but that it enhances the potency of the toxin.\n          <\/jats:p>","DOI":"10.1128\/iai.00733-15","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T01:01:53Z","timestamp":1438045313000},"page":"3982-3988","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep"],"prefix":"10.1128","volume":"83","author":[{"given":"Sai A.","family":"Batra","sequence":"first","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudarvili","family":"Shanthalingam","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard R.","family":"Munske","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genomics Core, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bindu","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abirami","family":"Kugadas","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jegarubee","family":"Bavanthasivam","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K.","family":"Highlander","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subramaniam","family":"Srikumaran","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(00)01262-4"},{"key":"e_1_3_2_3_2","first-page":"330","volume-title":"Infectious diseases of wild mammals","author":"Miller MW","year":"2008","unstructured":"Miller MW. 2008. Pasteurellosis, p 330\u2013339. In Williams ES, Barker IK (ed), Infectious diseases of wild mammals. 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