| Project title |
High throughput analysis of enterobacterial invasion |
| Summary |
Enterobacterial outer membrane proteins such as Hek, PagN and Tia (also known as PATH proteins) utilise mammalian, cell surface, heparinated-molecules to accomplish invasion of these cells. What is the molecular identity of these mammalian molecules and what signalling events are triggered in epithelial cells that facilitate bacterial entry mediated by PATH proteins? Furthermore, what is the nature of the interaction between the bacterial ligands and their receptors; specifically what amino acid sequences are required in PATH proteins for epithelial invasion?
To answer these questions the following experiments are underway
1. To adopt and adapt high-throughput fluorescent microscopy (Cellomics) in the analysis of microbial invasion of human epithelial cells.
2. To define the class of HSPG that PATH proteins bind to.
3. Define, at a molecular level, the sequences within PATH proteins that are required for HSPG-binding.
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| Funding Agency |
SFI |
| Programme |
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| Type of Project |
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| Date from |
1/10/10 |
| Date to |
1/10/14 |
| Person Months |
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| Project title |
E. coli sepsis; better treatment options using genomics |
| Summary |
Hypothesis 1
We have identified genes in pathogenic E. coli that protect the bacteria from serum killing in vivo. We hypothesize that these genes will be important in clinically-significant E. coli bloodstream infections in patients.
Hypothesis 2
We hypothesize that E. coli bloodstream isolates are becoming increasingly more virulent and resistant to antimicrobials.
Aims
The aim of this proposal is to measure gene expression of pathogenic E. coli from patient blood samples. We will ascertain if the induction of particular bacterial genes during infection is clinically significant. In parallel with this approach we will continue to gather large amounts of genotypic information on each bacterial isolate using microarray technologies.
Objectives
The main objectives will be to;
Measure the transcriptional responses of pathogenic E. coli exposed to complement-deficient serum.
Refine and enhance the virulence and resistance microarray.
Establish the SCOTS methodology in vitro
Apply SCOTS to patient samples
Determine if there is a correlation between the expression of protective genes in E. coli and clinical outcome.
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| Funding Agency |
HRB |
| Programme |
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| Type of Project |
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| Date from |
1/1/11 |
| Date to |
1/6/14 |
| Person Months |
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| Project title |
E. coli sepsis; better treatment options using genomics |
| Summary |
Hypothesis 1
We have identified genes in pathogenic E. coli that protect the bacteria from serum killing in vivo. We hypothesize that these genes will be important in clinically-significant E. coli bloodstream infections in patients.
Hypothesis 2
We hypothesize that E. coli bloodstream isolates are becoming increasingly more virulent and resistant to antimicrobials.
Aims
The aim of this proposal is to measure gene expression of pathogenic E. coli from patient blood samples. We will ascertain if the induction of particular bacterial genes during infection is clinically significant. In parallel with this approach we will continue to gather large amounts of genotypic information on each bacterial isolate using microarray technologies.
Objectives
The main objectives will be to;
Measure the transcriptional responses of pathogenic E. coli exposed to complement-deficient serum.
Refine and enhance the virulence and resistance microarray.
Establish the SCOTS methodology in vitro
Apply SCOTS to patient samples
Determine if there is a correlation between the expression of protective genes in E. coli and clinical outcome.
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| Funding Agency |
HRB |
| Programme |
|
| Type of Project |
|
| Date from |
1/1/11 |
| Date to |
1/6/14 |
| Person Months |
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| Sanjay H. Chotirmall, Stephen G. Smith, Cedric Gunaratnam, Sonya Cosgrove, Borislav D. Dimitrov, Shane J. O'Neill, Brian J. Harvey, Catherine M. Greene, Noel G. McElvaney, , Effect of Estrogen on Pseudomonas Mucoidy and Exacerbations in Cystic Fibrosis, The New England Journal of Medicine, 366, 2012, p1978 - 1986 |
| Cooke NM, Smith SG, Kelleher M, Rogers TR., Major differences exist in frequencies of virulence factors and multidrug resistance between community and nosocomial Escherichia coli bloodstream isolates., Journal of Clinical Microbiology, 48, 2010, p1099 - 1114 |
Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, ONeill SJ & McElvaney NG , TLR-induced inflammation in Cystic Fibrosis Epithelial Cells , Journal of Immunology, 174, 2005, p1638 - 1646
Url |
Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S & McElvaney NG , Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. , Journal of Immunology, 171, 2003, p931 - 937
Url |
| Regulation of virulence gene expression in bacterial pathogens in, editor(s)EA Groisman , Principles of Bacterial Pathogenesis, New York, Academic Press, 2001, [Dorman CJ & Smith SGJ ] |
| More Publications>>> |
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Last Updated:23-MAY-2013 |