Johne’s disease (JD) is a chronic enteric infection of cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP). The high economic cost and potential zoonotic threat of JD have driven efforts to develop tools and approaches to effectively manage this disease within livestock herds. Efforts to control JD through traditional animal management practices are complicated by MAP’s ability to cause long-term environmental contamination as well as difficulties associated with diagnosis of JD in the pre-clinical stages. As such, there is particular emphasis on the development of an effective vaccine. This is a daunting challenge, in large part due to MAP’s ability to subvert protective host immune responses. Accordingly, there is a priority to understand MAP’s interaction with the bovine host: this may inform rational targets and approaches for therapeutic intervention. Here we review the early host defenses encountered by MAP and the strategies employed by the pathogen to avert or subvert these responses, during the critical period between ingestion and the establishment of persistent infection in macrophages.

No abstract

Tools for conducting high-throughput kinome analysis do not exist for many species. For example, two commonly used techniques for monitoring phosphorylation events are phosphorylation-specific antibodies and peptide arrays. The majority of phosphorylation-specific antibodies are for human or mouse targets, and the construction of peptide arrays relies on information from phosphorylation databases, which are similarly biased toward human and mouse data. This is a substantial obstacle because many species other than mouse represent important biological models. On the basis of the observation that phosphorylation events are often conserved across species with respect to their relative positioning within proteins and their biological function, we demonstrate that it is possible to predict the sequence contexts of phosphorylation events in other species for the production of peptide arrays for kinome analysis. Through this approach, genomic information can be rapidly used to create inexpensive, customizable, species-specific peptide arrays for high-throughput kinome analysis. We anticipate that these arrays will be valuable for investigating the conservation of biological responses across species, validating animal models of disease, and translating research to clinical applications.