What the kinome reveals about resistance to foodborne pathogens.

Abstract

While the genetic similarities between vertebrates have been remarked on with each new complete genome sequenced, the physiological and phenotypic differences between agricultural species remain clear even to the casual observer. As one moves along the path of molecular biology, from DNA to RNA to protein, the distinctions between species increase. The separation between species further increases when the active sites of protein are considered. Phenotype is dictated by gene expression patterns, response to environmental stimuli, epigenetic alterations, protein translation, protein folding and interactions, post-translational modifications, and a host of other mechanisms. Post-translational modifications that mediate cellular signaling cascades and cellular response to stimuli are predominantly facilitated by protein kinases. Studying the changes in protein kinase activity is as close as we can come to studying phenotype and remain at a molecular level. Intracellular metabolic responses, specifically, depend on these kinase switches and are often transcriptionally independent; an organism must respond to the availability of nutrients and does not have time to engage the transcription and translation machinery to take up and consume sources of energy. Meanwhile the immune system often initiates responses through gene expression changes. Thus, studying kinase activity allows us to study metabolism alongside gene expression dependent responses such as most immune responses. Over many years of studying poultry in the context of foodborne pathogens, especially Salmonella species, a few kinase dependent pathways and energy sensors have emerged as critical to resistance or susceptibility. The central immunometabolic signaling hubs, such as PI3K-AKT-mTOR, have been shown to be part of the immunometabolic physiological responses key to resistance or susceptibility in chickens. Salmonella infections have a significant impact on kinases in these signaling hubs, while the most promising interventions modulate these hubs. Directing breeding selection criteria or feed additive interventions to these hubs and critical activating/deactivating control points is a promising approach in controlling these foodborne pathogens in poultry.