This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary focus of this proposal is the bacterial outer membrane protease IcsP (SopA), which is encoded by the virulence plasmid of the enteric pathogen Shigella flexneri. The involvement of IcsP in the pathogenicity of Shigella is poorly understood and warrants further investigation.
In specific aim 1, the regulation of icsP will be studied. A virulence gene activator, VirB, up-regulates the icsP promoter. A putative VirB-binding site has been identified within this DNA. This binding-site will be mutated by site-directed mutagenesis and the activity of the icsP promoter will be measured using a lacZ reporter. In vitro experiments will determine whether VirB binds to this site and characterize the mechanism of VirB-dependent regulation of the icsP promoter. Transcription of icsP and IcsP protein levels will be measured under a variety of physiological conditions encountered by Shigella in humans. These studies will provide further insight into how IcsP is regulated and may elucidate how IcsP functions in the pathogenicity of Shigella.
In specific aim 2, the possibility that IcsP plays additional roles in Shigella pathogenesis will be explored. The only known substrate of IcsP is another outer membrane protein IcsA. Preliminary data suggest IcsP proteolytically processes at least one other Shigella outer membrane protein. Using 2-D gel electrophoresis and proteomic approaches, this and other outer membrane proteins cleaved by IcsP will be identified. We expect that these studies will improve our understanding of the roles that IcsP plays during bacterial cell growth and differentiation in the host environment. Since proteases expressed by eukaryotes and prokaryotes differ considerably from one another, prokaryotic proteases offer an exciting possibility as targets for drug therapy. An enhanced understanding of IcsP and its role in Shigella growth and differentiation in host environments may allow us to assess whether drug-targeting of this family of proteases is feasible.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Nevada Reno
Schools of Medicine
United States
Zip Code
Agarwal, Andrea B; Feng, Cheng-Yuan; Altick, Amy L et al. (2016) Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons. Invest Ophthalmol Vis Sci 57:5576-5585
Etges, William J; de Oliveira, Cássia; Rajpurohit, Subhash et al. (2016) Preadult life history variation determines adult transcriptome expression. Mol Ecol 25:741-63
Kim, Kyung-Tai; Kim, Namhee; Kim, Hwan-Ki et al. (2016) ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons. Sci Rep 6:36491
Bjorke, Brielle; Shoja-Taheri, Farnaz; Kim, Minkyung et al. (2016) Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling. Neural Dev 11:18
Gorjala, P; Cairncross, J G; Gary, R K (2016) p53-dependent up-regulation of CDKN1A and down-regulation of CCNE2 in response to beryllium. Cell Prolif 49:698-709
Blumröder, R; Glunz, A; Dunkelberger, B S et al. (2016) Mcm3 replicative helicase mutation impairs neuroblast proliferation and memory in Drosophila. Genes Brain Behav 15:647-59
Braga, Marina Vianna; Pinto, Zeneida Teixeira; Queiroz, Margareth Maria de Carvalho et al. (2016) Effect of age on cuticular hydrocarbon profiles in adult Chrysomya putoria (Diptera: Calliphoridae). Forensic Sci Int 259:e37-47
Garcia, Juana; Sorrentino, Jacob; Diller, Emily J et al. (2016) A General Method for Nucleophilic Aromatic Substitution of Aryl Fluorides and Chlorides with Dimethylamine using Hydroxide-Assisted Decomposition of N,N-Dimethylforamide. Synth Commun 46:475-481
Etges, William J; Trotter, Meredith V; de Oliveira, Cássia C et al. (2015) Deciphering life history transcriptomes in different environments. Mol Ecol 24:151-79
Snodgrass, Casey J; Burnham-Marusich, Amanda R; Meteer, John C et al. (2015) Conserved ion and amino acid transporters identified as phosphorylcholine-modified N-glycoproteins by metabolic labeling with propargylcholine in Caenorhabditis elegans cells. Glycobiology 25:403-11

Showing the most recent 10 out of 279 publications