Oral Presentation The 3rd Prato Conference on the Pathogenesis of Bacterial Diseases of Animals 2014

Understanding the Pathogenic Mechanisms of Mycobacterium avium paratuberculosis through the Development and Application of Species-Specific Peptide Arrays for Kinome Analysis (#60)

Scott Napper 1 , Ryan Arsenault 2 , Brett Trost 1 , Anthony Kusalik 3 , Philip Griebel 1
  1. Vaccine and Infectious Disease Organization, Saskatoon, SASK, Canada
  2. - Agricultural Research Service (USDA-ARS), Southern Plains Agricultural Research Center (SPARC), United States Department of Agriculture - Agricultural Research Service (USDA-ARS), College Station, Texas, USA
  3. Computer Science, University of Saskatchewan , Saskatoon, Saskatchewan, Canada

Cellular responses are often mediated at the level of reversible, kinase-mediated protein phosphorylation. Understanding these dynamic patterns of phosphorylation has proven a useful approach to understand complex biology, identify biomarkers and detect therapeutic targets. Unfortunately, until recently, the tools required for global analysis of cellular kinase (kinome) activity have not been available for livestock species. Through the development of software platforms that enable the generation and analysis of species-specific peptide arrays our group has developed and applied kinome analysis to biological questions of a number of livestock species including cattle, pigs, horses, chickens and honeybees1. Priority application of the species-specific arrays has been in defining host responses to infectious challenge. For example, through the development of a bovine-specific peptide array our group is investigating host responses associated with Johne’s disease. Through characterization of signaling responses induced in isolated bovine monocytes by infection with Mycobacterium avium subspecies paratuberculosis (MAP) we have identified the mechanisms employed by the pathogen to subvert two critical host defensive signaling pathways (Toll-like receptors2 and interferon gamma3) as well as identifying a potential therapeutic target. More recent application of the arrays to intestinal tissues from a MAP infection model4 further highlights the strategies employed by MAP to influence host immune responses at the site of infection in order to establish chronic infection5,6.

  1. Arsenault R, Griebel P. and Napper S. (2011) Peptide Arrays for Kinome Analysis: New Opportunities and Remaining Challenges. Proteomics. 24:4595-609.
  2. Arsenault R, Li Y, Maattanen P, Scruten E, Doig K, Potter A, Griebel P, Kusalik A. and Napper S. (2013) Altered Toll-like receptor 9 signaling in Mycobacterium avium subsp. paratuberculosis-infected bovine monocytes reveals potential therapeutic targets. Infect Immun. 81:226-37.
  3. Arsenault R, Li Y, Bell K, Doig K, Potter A, Griebel PJ, Kusalik A. and Napper S. (2012) Mycobacterium avium subsp. paratuberculosis inhibits gamma interferon-induced signaling in bovine monocytes: insights into the cellular mechanisms of Johne's disease. Infect. Immun. 80:3039-48.
  4. Charavaryamath C, Gonzalez-Cano P, Fries P, Gomis S, Doig K, Scruten E, Potter A, Napper S. and Griebel P. (2013) Host responses to persistent Mycobacterium avium subspecies paratuberculosis infection in surgically isolated bovine ileal segments. Clin. Vaccine Immunol. 2:156-65.
  5. Määttänen P, Trost B, Scruten E, Potter A, Kusalik A, Griebel P. and Napper S. (2013) Divergent immune responses to Mycobacterium avium subsp. paratuberculosis infection correlate with kinome responses at the site of intestinal infection. Infect. Immun. 81:2861-72.
  6. Arsenault R, Maattanen P, Daigle J, Potter A, Griebel P. and Napper S. (2014) From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium avium subsp. Paratuberculosis. Vet. Res. 45:54