Study examines early mechanisms of infection by Salmonella

Vancouver, BC – Molecular research company Kinexus Bioinformatics has published the results of a major study to investigate the host signalling pathways impacted by Salmonella enterica. The study, which was undertaken in collaboration with researchers at the Centre for High Throughput Biology at the University of British Columbia (UBC) was published in the journal Science Signaling.

Mass spectrometric analyses revealed that more than 24% of 9,500 phosphorylation sites tracked in human cells were significantly altered with 20 minutes of Salmonella infection. Phosphosites often function as on/off switches to regulate intracellular communication systems and their phosphorylation is catalyzed by protein kinases. Application of Kinexus’ 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 kinase 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.

Over 100,000 human phosphosites in over 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 6,000 previously unknown phosphosites, and these have been posted for open access on the Kinexus PhosphoNET website (http://www.phosphonet.ca).

“The mass spectrometry analyses were performed at the Centre for High Throughput Biology at UBC, and the work represents one of the major studies of this kind undertaken to date,” said Dr Steven Pelech, president and chief scientific officer of Kinexus and a professor in the Department of Medicine at the University of British Columbia. “In combination with the predictive algorithms developed at Kinexus, it is becoming possible to map out the complex architecture of cell signalling networks and identify the sites of action of toxins that are produced by pathogenic viruses and bacteria.”