title: Bighorn sheep × domestic sheep hybrids survive Mannheimia haemolytica challenge in the absence of vaccination.
abstract: Bighorn sheep (BHS, Ovis canadensis) are much more susceptible than domestic sheep (DS, Ovis aries) to pneumonia caused by leukotoxin (Lkt)-producing members of the Family Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi. Leukotoxin is widely accepted as the critical virulence factor of these bacteria since Lkt-negative mutants do not cause death of BHS. Typically, DS carry Lkt-positive M. haemolytica and/or B. trehalosi as commensal bacteria in their nasopharynx. In contrast, most BHS do not carry Lkt-positive M. haemolytica or B. trehalosi, or carry Lkt-negative strains in their nasopharynx. In previous studies, we demonstrated that unimmunized DS resist M. haemolytica challenge while BHS succumb to it. We hypothesized that Lkt-neutralizing antibodies, induced by Lkt-positive M. haemolytica and/or B. trehalosi innately carried by DS in their nasopharynx, render them less susceptible to infection by these bacteria. In this study we developed BHS×DS F1 hybrids by artificial insemination of domestic ewes with BHS semen. F1 hybrids were fertile, and produced F2 hybrids and back-crosses. The F1, F2, and back-crosses were raised together with domestic ewes. All these animals acquired Lkt-positive M. haemolytica and/or B. trehalosi, and developed high titers of Lkt-neutralizing antibodies in the absence of vaccination. Furthermore, all of these animals resisted challenge with lethal dose of M. haemolytica. These results suggest that lack of previous exposure to Lkt is at least partially responsible for fatal pneumonia in BHS when they acquire Lkt-positive M. haemolytica and/or B. trehalosi from DS when the two species commingle.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: R
authors.initials: R
authors.lastname: Subramaniam
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shanthalingam
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bavananthasivam
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kugadas
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: B
authors.initials: B
authors.lastname: Raghavan
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Batra
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Herndon
authors.affiliation: Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tibary
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: D
authors.initials: D
authors.lastname: Nelson
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA; Washington Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Potter
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Foreyt
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. Electronic address: ssrikumaran@vetmed.wsu.edu.
authors.forename: S
authors.initials: S
authors.lastname: Srikumaran
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D004198:Disease Susceptibility / Q000276:immunology / Q000662:veterinary*; D005098:Exotoxins / Q000276:immunology; D005260:Female; D006824:Hybridization, Genetic / Q000276:immunology*; D016978:Mannheimia haemolytica; D009305:Nasopharynx / Q000382:microbiology; D016871:Pasteurellaceae Infections / Q000276:immunology / Q000662:veterinary*; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology* / Q000382:microbiology; D034581:Sheep, Bighorn / Q000276:immunology; D034561:Sheep, Domestic / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D005098:Exotoxins; C018579:leukotoxin
keywords: BHS×DS hybrid; Leukotoxin; M. haemolytica; Pneumonia