title: Comparative Genomic Analysis of Mannheimia haemolytica from Bovine Sources.
abstract: Bovine respiratory disease is a common health problem in beef production. The primary bacterial agent involved, Mannheimia haemolytica, is a target for antimicrobial therapy and at risk for associated antimicrobial resistance development. The role of M. haemolytica in pathogenesis is linked to serotype with serotypes 1 (S1) and 6 (S6) isolated from pneumonic lesions and serotype 2 (S2) found in the upper respiratory tract of healthy animals. Here, we sequenced the genomes of 11 strains of M. haemolytica, representing all three serotypes and performed comparative genomics analysis to identify genetic features that may contribute to pathogenesis. Possible virulence associated genes were identified within 14 distinct prophage, including a periplasmic chaperone, a lipoprotein, peptidoglycan glycosyltransferase and a stress response protein. Prophage content ranged from 2-8 per genome, but was higher in S1 and S6 strains. A type I-C CRISPR-Cas system was identified in each strain with spacer diversity and organization conserved among serotypes. The majority of spacers occur in S1 and S6 strains and originate from phage suggesting that serotypes 1 and 6 may be more resistant to phage predation. However, two spacers complementary to the host chromosome targeting a UDP-N-acetylglucosamine 2-epimerase and a glycosyl transferases group 1 gene are present in S1 and S6 strains only indicating these serotypes may employ CRISPR-Cas to regulate gene expression to avoid host immune responses or enhance adhesion during infection. Integrative conjugative elements are present in nine of the eleven genomes. Three of these harbor extensive multi-drug resistance cassettes encoding resistance against the majority of drugs used to combat infection in beef cattle, including macrolides and tetracyclines used in human medicine. The findings here identify key features that are likely contributing to serotype related pathogenesis and specific targets for vaccine design intended to reduce the dependency on antibiotics to treat respiratory infection in cattle.
authors.affiliation: Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB T1J 4B1, Canada.|Department of Large Animal Clinial Science, Western Colledge of Verterinary Medicine, University of Saskatoon, Saskatoon, Canada.
authors.forename: Cassidy L
authors.initials: CL
authors.lastname: Klima
authors.affiliation: Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB T1J 4B1, Canada.
authors.forename: Shaun R
authors.initials: SR
authors.lastname: Cook
authors.affiliation: Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB T1J 4B1, Canada.
authors.forename: Rahat
authors.initials: R
authors.lastname: Zaheer
authors.affiliation: Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Lethbridge, Alberta, Canada.
authors.forename: Chad
authors.initials: C
authors.lastname: Laing
authors.affiliation: Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Lethbridge, Alberta, Canada.
authors.forename: Vick P
authors.initials: VP
authors.lastname: Gannon
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB T1J 4B1, Canada.
authors.forename: Jay
authors.initials: J
authors.lastname: Rasmussen
authors.affiliation: Vaccine and Infectious Disease Organization, Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Potter
authors.affiliation: Department of Large Animal Clinial Science, Western Colledge of Verterinary Medicine, University of Saskatoon, Saskatoon, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Hendrick
authors.affiliation: Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB T1J 4B1, Canada.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Alexander
authors.affiliation: Agriculture and Agri-Food Canada Research Centre, Lethbridge, AB T1J 4B1, Canada.
authors.forename: Tim A
authors.initials: TA
authors.lastname: McAllister
mesh_terms: D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D002417:Cattle; D021901:DNA, Intergenic / Q000235:genetics; D016680:Genome, Bacterial; D016978:Mannheimia haemolytica / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010802:Phylogeny; D039002:Prophages / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D021901:DNA, Intergenic