Phosphoproteomics Mass Spectrometry Study Provides Insights into Early Mechanisms of Infection by Salmonella

Scientists at Kinexus Bioinformatics Corporation (Vancouver, British Columbia, Canada), in collaboration with researchers at the Centre for High Throughput Biology at the University of British Columbia (Vancouver, British Columbia, Canada), investigated the host signaling pathways that are affected by Salmonella enterica, a food-borne bacteria that is a leading cause of food poisoning in North America and around the world. The results of the study, using mass spectrometric analyses, revealed that more than 24 percent of 9500 phosphorylation sites tracked in human cells were significantly altered with 20 minutes of Salmonella infection.

Application of Kinexus’s Kinase Predictor algorithm for 493 human protein kinases against each of the top Salmonella-affected phosphosites permitted identification of specific protein kinases that are affected by Salmonella, including the proto-oncogene-encoded protein kinases Pim1. Specific inhibition of Pim1 in follow-up studies was found to mitigate some of the pathogen effects of this bacteria, and implicated this kinase as a possible target for therapeutic drug intervention.

More than 100,000 human phosphosites in more than 14,000 of the 23,000 proteins encoded by the human genome have now been experimentally confirmed. This study has led to the identification of over 6000 previously unknown phosphosites, and these have been posted for open access on the Kinexus PhosphoNET website www.chromatographyonline.com