Pathogenic Shigellae and Yersiniae are one ofthe leading causes of foodborne diseases. While these diseases can be theoretically treated with antibiotics, the high incidence of the multidrug-resistant strains means that development of new antimicrobial treatments is critical. Bacteria corrupt numerous biochemical pathways of the host and understanding of these mechanisms directly contributes to the novel target drug discovery as well as it facilitates research on the established drug targets. However, many important aspects ofthe bacteria-host protein interactions remain unknown. Deubiquitinating enzymes (DUBs) regulate ubiquitination, a reversible modification that controls protein function, stability and localization. Our long-term goal is to understand the functions of DUBs in bacterial infection in order to facilitate discovery of novel therapies and diagnostics. The overall objective in this proposal is to determine the functions of DUBs in the foodborne diseases caused by Shigella and Yersinia by using an integrated proteomics approach and functional studies. Our central hypothesis is that human DUBs, such as 0TUB1, and their associated protein networks are central to virulence in shigellosis and yersiniosis, and that DUB activity is regulated by bacteria and host, consequently determining the disease outcome. Assessment of DUB-associated protein networks and their role in pathogenesis is novel and innovative. We will use two very different enteropathogens to unveil conserved as well as strain-specific biological functions of the DUBs. The rationale for the proposed research is that once we know functions and downstream pathways of DUBs affected by these infections, we can quantify the relevance of DUBs to these diseases and apply this information to a rational drug design.
This comprehensive study of deubiquitinating enzymes involved in infections with Shigella and Yersinia will provide characterization of novel host responses to enterobacterial infections and insights into the hostpathogen interplay. It signifies an importance for translational medicine due to its contribution to finding protein targets for new chemotherapeutics, clearly required for an effective treatment of these infectious diseases.
|Wilson, Gillian J; Tuffs, Stephen W; Wee, Bryan A et al. (2018) Bovine Staphylococcus aureus Superantigens Stimulate the Entire T Cell Repertoire of Cattle. Infect Immun 86:|
|Hui, Winnie W; Hercik, Kamil; Belsare, Sayali et al. (2018) Salmonella enterica Serovar Typhimurium Alters the Extracellular Proteome of Macrophages and Leads to the Production of Proinflammatory Exosomes. Infect Immun 86:|
|Lee, Juyeun; Park, Nogi; Park, Joo Youn et al. (2018) Induction of Immunosuppressive CD8+CD25+FOXP3+ Regulatory T Cells by Suboptimal Stimulation with Staphylococcal Enterotoxin C1. J Immunol 200:669-680|
|Nakamya, Mary F; Ayoola, Moses B; Park, Seongbin et al. (2018) The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression. Med Sci (Basel) 6:|
|Wen, Feng; Li, Lei; Zhao, Nan et al. (2018) A Y161F Hemagglutinin Substitution Increases Thermostability and Improves Yields of 2009 H1N1 Influenza A Virus in Cells. J Virol 92:|
|Kaplan, Barbara L F (2018) Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis. Curr Protoc Toxicol 75:11.25.1-11.25.22|
|Wen, Feng; Blackmon, Sherry; Olivier, Alicia K et al. (2018) Mutation W222L at the Receptor Binding Site of Hemagglutinin Could Facilitate Viral Adaption from Equine Influenza A(H3N8) Virus to Dogs. J Virol 92:|
|Varela-Stokes, A S; Park, S H; Stokes, J V et al. (2018) Tick microbial communities within enriched extracts of Amblyomma maculatum. Ticks Tick Borne Dis 9:798-805|
|Lee, Jung Keun; Stokes, John V; Moraru, Gail M et al. (2018) Transmission of Amblyomma maculatum-Associated Rickettsia spp. During Cofeeding on Cattle. Vector Borne Zoonotic Dis 18:511-518|
|Ammari, Mais; McCarthy, Fiona; Nanduri, Bindu (2018) Leveraging Experimental Details for an Improved Understanding of Host-Pathogen Interactome. Curr Protoc Bioinformatics 61:8.26.1-8.26.12|
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