Serotype variability, genomic plasticity and increasing antibiotic resistance of S. pneumoniae, pose considerable challenges for designing intervention strategies for this global public health concern. There is a need for the identification as well as characterization of novel vaccine candidates for effective immunization against pneumococcus, as the available vaccines are not effective against all serotypes. Polyamines are ubiquitous small cationic molecules necessary for pneumococcal growth and virulence. Therefore, intracellular polyamine levels are tightly regulated, thus making polyamine transport mechanisms a highly attractive focus for investigation on pathogenesis and immune responses. Our preliminary results indicate that impaired polyamine transport causes attenuation of pneumonia in mouse models. However, the pathogen-host interactions responsible for this attenuation are yet to be characterized. Our central hypothesis is that attenuation in pneumococcal pneumonia by impaired pneumococcal polyamine transport is due to the reduced virulence factor gene expression and/or reduced resistance to host innate immune responses. We will test this hypothesis by conducting the following specific aims.
Specific aims : 1-identify polyamine responsive pneumococcal genes and pathways by comparing gene expression of wild type and ApotABCD S. pneumoniae (a strain with genetic deletion of polyamine transport operon) in a mouse model of pneumonia;2-determine the host innate immune responses to polyamine deficient pneumococcus by measuring the expression of antimicrobial proteins, acute phase proteins, opsonophagocytosis by macrophages and neutrophils, and host signaling pathways and functions including Toll-like receptor signaling, using proteomics. Successful completion ofthe proposed studies will identify the pneumococcal molecular mechanisms responsive to polyamine transport as well as specific host innate immune responses. Project results will shed light on the role of polyamines in infectious diseases in general for the identification of unique intra and extracellular targets for design of novel vaccines or therapeutics in future.
Streptococcus pneumoniae is the most common cause of community acquired pneumonia and a leading cause of meningitis, sinusitis, chronic bronchitis, and otitis media. An estimated 570,000 cases of pneumococcal pneumonia occur annually in the United States alone. Deficiencies in polyamine transport cause attenuation of virulence of pneumonia. Polyamine transport genes that appear to be conserved within the soecies. provide a potential new class of broad-based vaccine candidates or therapeutic targets
|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
Showing the most recent 10 out of 57 publications