Discovery of Host Proteins Involved in Host-Pathogen Interactions
EMSL Project ID
47623
Abstract
The multiple mechanisms by which pathogenic enterobacteria of the genus Salmonella infect their host indicate a complex host-pathogen relationship. The pathogen secretes dozens of proteins, termed 'effectors', in an organized strategy to modulate host cell function and evade the host immune response to enable colonization of the host. Recently, we discovered more than 50 new secreted proteins presumably deployed by Salmonella to subvert host cell defense mechanisms, bringing the total number of identified putative secreted effectors to nearly 100. Identifying the host proteins targeted by these putative effectors and determining the nature of these interactions will enable development and testing of mechanistic hypotheses about their modes of action. Our research plan employs a novel high throughput proteomic screening approach to identify effector and host proteins involved in specific host-pathogen interactions and to elucidate the underlying molecular mechanisms behind these interactions. As part of this plan, we will collaborate with the Protein Structure Initiative 3 (PSI:Biology) network to generate essential structural information to help define the mechanisms by which the pathogen modulates or disrupts host cell functions. The long-term goal is to identify novel therapeutic targets and develop new tools for manipulating the host cell response to infection.
Project Details
Start Date
2012-09-07
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members
Related Publications
Conlon BP, ES Nakayasu, LE Fleck, MD LaFleur, VM Isabella, K Coleman, SN Leonard, RD Smith, JN Adkins, and K Lewis. 2013. "Activated ClpP kills persisters and eradicates a chronic biofilm infection." Nature 503(7476):365-370. doi:10.1038/nature12790
Li J, ES Nakayasu, CC Overall, R Johnson, AS Kidwai, JE McDermott, C Ansong, F Heffron, E Cambronne, and JN Adkins. 2015. "Global analysis of Salmonella alternative sigma factor E on protein translation." Journal of Proteome Research 14(4):1716-1726. doi:10.1021/pr5010423
Nakayasu ES, MA Sydor, RN Brown, T Sobreira, GW Slysz, DR Humphrys, T Skarina, O Onoprienko, R Di Leo, BLD Kaiser, J Li, E Cambronne, RD Smith, A Savchenko, and JN Adkins. 2015. "Identification of Salmonella Typhimurium deubiquitinase SseL substrates by immunoaffinity enrichment and quantitative proteomic analysis." Journal of Proteome Research . doi:10.1021/acs.jproteome.5b00574 [In Press]