Characterization of Effector and Host Proteins Involved in Host-Pathogen Interactions
EMSL Project ID
42696
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
Project type
Exploratory Research
Start Date
2011-04-05
End Date
2012-04-08
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Elfenbein JR, LA Knodler, ES Nakayasu, C Ansong, HM Brewer, L Bogomolnaya, LG Adams, M McClelland, JN Adkins, and HL Andrews-Polymenis. 2015. "Multicopy single-stranded DNA directs intestinal colonization of enteric pathogens." PLoS Genetics 11(9):e1005472. doi:10.1371/journal.pgen.1005472
Merkley ED, ES Baker, KL Crowell, DJ Orton, T Taverner, C Ansong, YM Ibrahim, MC Burnet, JR Cort, GA Anderson, RD Smith, and JN Adkins. 2013. "Mixed-Isotope Labeling with LC-IMS-MS for Characterization of Protein-Protein Interactions by Chemical Cross-Linking ." Journal of the American Society for Mass Spectrometry. doi:10.1007/s13361-012-0565-x
Merkley ED, JR Cort, and JN Adkins. 2013. "Cross-Linking and Mass Spectrometry Methodologies to Facilitate Structural Biology: Finding a Path through the Maze." Journal of Structural and Functional Genomics 14(3):77-90. doi:10.1007/s10969-013-9160-z
Merkley ED, S Rysavy, A Kahraman, RP Hafen, V Daggett, and JN Adkins. 2014. "Distance Restraints from Cross-Linking Mass Spectrometry: Mining a Molecular Dynamics Simulation Database to Evaluate Lysine-Lysine Distances." Protein Science Epub Ahead of Print:, doi:10.1002/pro.2458
Nakayasu ES, C Ansong, JN Brown, F Yang, D Lopez-Ferrer, W Qian, RD Smith, and JN Adkins. 2013. "Evaluation of selected binding domains for the analysis of ubiquitinated proteomes." Journal of the American Society for Mass Spectrometry. doi:10.1007/s13361-013-0619-8. Epub ahead of print
Sontag RL, C Mihai, G Orr, A Savchenko, T Skarina, H Cui, JR Cort, JN Adkins, and RN Brown. 2015. "Electroporation of Functional Bacterial Effectors into Mammalian Cells." Journal of Visualized Experiments 95(1):e52296. doi:10.3791/52296
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