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Dr Stephen Smith B.A. Ph.D

photoofmeDept of Clinical Microbiology, School of Medicine

Trinity College Dublin

Room 125 Sir Patrick Dun Laboratories (Map) Central Pathology Lab, St James's Hospital

Dublin 8

353-1-896-8590 sgsmith@tcd.ie

 

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Research Projects

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ETEC

Regulation of virulence gene expression in enterotoxigenic E. coli ETEC Fimbriae are essential in the pathogenesis of diarrheal disease caused by the global pathogen ETEC. Fimbrial synthesis is positively regulated by AraC-type regulators. We have focused on the Rns family of regulators and are carrying out structure functional analyses of these proteins.

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cover from Microbiology September 2010, further details here

ExPEC

Virulence of Meningitic E. coli We have identified the Hek protein as being an adhesin and invasin for meningitic E. coli.We have deduced that loop 2 of this protein is responsible for adhesion and invasion. Loop2 is absolutely required for binding to host HSPG molecules. Intriguingly, this loop is also involved in auto-aggregation. We have also carried out a proteomic analysis of the OmpA and IbeB proteins of meningitic E. coli to assess their contribution to the proteome.

 

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We are also examining alternative mechanisms for serum resistance of ExPEC.

 

Salmonella

Analysis of Salmonella invasion and adhesion Using proteomics and bioinformatics we have identified a number of new factors involved in Salmonella adhesion. We have focused extensively on the PagN outer membrane protein and have shown it to be PhoP regulated and induced in macrophages. PagN mediates adhesion to epithelial cells and macrophages.

 

Funding sources

Science Foundation Ireland

Health Research Board

Staff

Dr Helen Miajlovic - postdoc

Graduate students

Samantha Pare

Clodagh Murphy

 

Representative publications

Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique Tidi Hassan, Stephen G. J. Smith, Kevin Gaughan, Irene K. Oglesby, Shane O Neill, Noel G. McElvaney, and Catherine M. GreeneNucl. Acids Res. first published online January 15, 2013 doi:10.1093/nar/gks1466

Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. Chotirmall SH, Smith SG, Gunaratnam C, Cosgrove S, Dimitrov BD, O'Neill SJ, Harvey BJ, Greene CM, McElvaney NG. N Engl J Med. 2012 May 24;366(21):1978-86

Snap denaturation reveals dimerization by AraC-like protein Rns, Vivienne Mahon, Robert P. Fagan, Stephen G.J. Smith Biochimie 94 (2012), pp. 2058-2061

A novel role for SarX in Staphylococcus epidermidis biofilm regulation. Rowe SE, Mahon V, Smith SG, O'Gara JP. Microbiology. 2011 Apr;157(Pt 4):1042-9.

Crossman LC, Chaudhuri RR, Beatson SA, Wells TJ, Desvaux M, Cunningham AF,Petty NK, Mahon V, Brinkley C, Hobman JL, Savarino SJ, Turner SM, Pallen MJ, Penn CW, Parkhill J, Turner AK, Johnson TJ, Thomson NR, Smith SG, Henderson IR. A commensal gone bad: complete genome sequence of the prototypical enterotoxigenic
Escherichia coli strain H10407. J Bacteriol. 2010 Nov;192(21):5822-31.
PubMed PMID: 20802035.

Mahon V, Smyth CJ, Smith SG. Mutagenesis of the Rns regulator of enterotoxigenic Escherichia coli reveals roles for a linker sequence and twohelix-turn-helix motifs. Microbiology. 2010 Sep;156(Pt 9):2796-806.

Cooke NM, Smith SG, Moran GP, Cooke FJ, Ivens A, Wain J, Rogers TR. Comparison of two DNA microarrays for detection of plasmid-mediated antimicrobial resistance and virulence factor genes in clinical isolates of Enterobacteriaceae and non-Enterobacteriaceae. Walsh F, Int J Antimicrob Agents. 2010 Mar 29

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. J Clin Microbiol. 2010 Apr;48(4):1099-104.

Emer P. Reeves, Michael Williamson, Barry Byrne, David A. Bergin, Stephen G. J. Smith, Peter Greally, Richard O’Kennedy, Shane J. O’Neill, and Noel G. McElvaney IL-8 Dictates Glycosaminoglycan Binding and Stability of IL-18 in Cystic Fibrosis J. Immunol., Feb 2010; 184: 1642 - 1652.

Lambert MA, Smith SG.The PagN protein mediates invasion via interaction with proteoglycan.FEMS Microbiol Lett. 2009 Jun 3.

PMID: 19552707

CM. Greene and S.G. J. Smith Microbial Recognition by Epithelium pp169-185 in The Pulmonary Epithelium in Health and Disease, David Proud (Editor) ISBN: 978-0-470-05951-7 2008 John Wiley & Sons, Ltd

Lambert MA, Smith SG. The PagN protein of Salmonella enterica serovar Typhimurium is an adhesin and invasin. BMC Microbiol. 2008 Sep 8;8:142.

Fagan RP, Lambert MA, Smith SG. The hek outer membrane protein of Escherichia coli strain RS218 binds to proteoglycan and utilizes a single extracellular loop for adherence, invasion, and autoaggregation. Infect Immun. 2008 Mar;76(3):1135-42

S. Molan, S. Smith, T. R. Rogers, F. Walsh Antimicrobial resistance mechanisms in clinical isolates of Pseudomonas aeruginosa.. Clinical Microbiology and Infection. 2008 May; 14 (s7): P2099.

N. Cooke, S. Smith, T. Rogers Molecular characterisation of antimicrobial resistant bacteraemic Escherichia coli isolates from an Irish hospital Clinical Microbiology and Infection 2008 May; 14 (s7): P2109.

Smith SG, Mahon V, Lambert MA, Fagan RP. A molecular Swiss army knife: OmpA structure, function and expression. FEMS Microbiol Lett. 2007 Aug;273(1):1-11.

Fagan RP, Smith SG.The Hek outer membrane protein of Escherichia coli is an auto-aggregating adhesin and invasin. FEMS Microbiol Lett. 2007 Apr;269(2):248-55.

Kelly A, Conway C, O Croinin T, Smith SG, Dorman CJ. DNA supercoiling and the Lrp protein determine the directionality of fim switch. DNA inversion in Escherichia coli K-12. J Bacteriol. 2006 Aug;188:5356-63

Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, Griffin S, O'neill SJ, McElvaney NG. TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells. J Immunol. 2005 174:1638-46.

Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S, McElvaney NG. Inactivation of human b-defensins 2 and 3 by elastolytic cathepsins.J Immunol 2003 171:931-7.

 


Last updated 23 November 2016 Stephen Smith (Email).