Stephen Smith
Associate Professor, Clinical Microbiology

Publications and Further Research Outputs

Peer-Reviewed Publications

Helen Miajlovic, Micheál Mac Aogáin, Cathal J. Collins, Thomas R. Rogers, Stephen G. J. Smith, Characterization of Escherichia coli bloodstream isolates associated with mortality, Journal of Medical Microbiology, 65, (1), 2016, p71-79 Journal Article, 2016 URL

Miche􏰀al Mac Aog􏰀ain, Helen Miajlovic, Geraldine Moloney, Sanjay H. Chotirmall, Thomas R. Rogers and Stephen G. J. Smith, Identification of a novel sequence type of Escherichia coli as the causative agent of pyelonephritis and bloodstream infection, JMM Case Reports, 3, 2016, p1 - 4 Journal Article, 2016 DOI URL TARA - Full Text

C.M. Murphy, S. Paré, G. Galea, J.C. Simpson, S.G.J. Smith ,, Accurate and semi-automated analysis of bacterial association with mammalian cells, Journal of Microbiological Methods, 122, 2016, p8 - 12 Journal Article, 2016 URL

R. D. Moriarty, A. Cox, M. McCall, S. G. J. Smith, D. Cox1, Escherichia coli induces platelet aggregation in an FcγRIIa-dependent manner, Journal of Thrombosis and Haemostasis, 14, 2016, p1 - 10 Journal Article, 2016 URL

miR-CATCH: MicroRNA Capture Affinity Technology in, editor(s)Mouldy Sioud , RNA Interference: Challenges and Therapeutic Opportunities, Methods in Molecular Biology,, Springer, 2015, pp365 - 373, [Sebastian Vencken, Tidi Hassan, Noel G. McElvaney, Stephen G.J. Smith, Catherine M. Greene] Book Chapter, 2015

Miajlovic H, Smith SG., Bacterial self-defence: how Escherichia coli evades serum killing., FEMS Microbiol Lett., 354, 2014, p1 - 9 Journal Article, 2014 TARA - Full Text

Pares S, Smith SG, Functional Analysis of the PagN protein of Salmonella enterica , American Society for Microbiology, Boston, 16/05/2014, 2014 Poster, 2014

Miajlovic H, Cooke NM, Moran GP, Rogers TR, Smith SG., Response of Extraintestinal Pathogenic Escherichia coli to Human Serum Reveals a Protective Role for Rcs-Regulated Exopolysaccharide Colanic Acid., Infect Immun, 2014, p298 - 205 Journal Article, 2014 TARA - Full Text

Hassan T, Smith SG, Gaughan K, Oglesby IK, O'Neill S, McElvaney NG, Greene CM., Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique., Nucleic Acids Research, 41, (6), 2013, pe71 Journal Article, 2013 TARA - Full Text

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 Journal Article, 2012

Vivienne Mahon, Robert P. Fagan, Stephen G.J. Smith, Snap denaturation reveals dimerization by AraC-like protein Rn, Biochimie, 94, 2012, p2058 - 2061 Journal Article, 2012

Rowe SE, Mahon V, Smith SG, O'Gara JP, A novel role for SarX in Staphylococcus epidermidis biofilm regulation, Microbiology, 157, (4), 2011, p1042 - 1049 Journal Article, 2011

15. Chotirmall SH, Smith SG, Gunaratnam C, Cosgrove S, Dimitrov BD, O'Neill SJ, Harvey BJ, Greene CM, McElvaney NG. , Estrogen Induces Mucoid Conversion of Pseudomonas aeruginosa and Promotes Infective Exacerbations in Females with Cystic Fibrosis. , Irish Journal of Medical Science , 180, 2011, p453 - 454 Journal Article, 2011

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, 156, 2010, p2796 - 2806 Journal Article, 2010

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 Journal Article, 2010

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., Journal of Bacteriology, 192, 2010, p5822 - 5831 Journal Article, 2010 TARA - Full Text

Walsh F, 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, International Journal of Antimicrobial Agents, pending, (pending), 2010 Journal Article, 2010 TARA - Full Text

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, 184, 2010, p1642 - 1652 Journal Article, 2010

Lambert MA, Smith SG., The PagN protein mediates invasion via interaction with proteoglycan., FEMS Microbiol Lett., 2009, p209 - 216 Journal Article, 2009

Lambert MA, Smith SG, The PagN protein of Salmonella enterica serovar Typhimurium is an adhesin and invasin. , BMC Microbiol, 8, 2008, p142 - 142 Journal Article, 2008

S. Molan, S. Smith, T. R. Rogers, F.Walsh, Walsh Antimicrobial resistance mechanisms in clinical isolates of Pseudomonas aeruginosa.. , Clinical Microbiology and Infection, 14(s7), 2008, p2209 - 2209 Journal Article, 2008

N. Cooke, S. Smith, T. Rogers, Molecular characterisation of antimicrobial resistant bacteraemic Escherichia coli isolates from an Irish hospital , Clinical Microbiology and Infection, 2008, p2109 - 2109 Journal Article, 2008

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, 76, 2008, p1135 - 1142 Journal Article, 2008

Fagan RP, Smith SG, The Hek outer membrane protein of Escherichia coli is an auto-aggregating adhesin and invasin, FEMS Microbiol Lett, 269, 2007, p248 - 255 Journal Article, 2007

Smith SG, Mahon V, Lambert MA, Fagan RP., A molecular Swiss army knife: OmpA structure, function and expression., FEMS Microbiol Lett, 273, 2007, p1 - 11 Journal Article, 2007

Kelly A, C Conway, T O Croinin, SGJ Smith, CJ Dorman, DNA supercoiling and the Lrp protein determine the directionality of fim switch DNA inversion in Escherichia coli K-12, Journal of Bacteriology, 188, (15), 2006, p5356 - 5363 Journal Article, 2006 TARA - Full Text DOI

Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, O'Neill SJ & McElvaney NG , TLR-induced inflammation in Cystic Fibrosis Epithelial Cells , Journal of Immunology, 174, 2005, p1638 - 1646 Journal Article, 2005 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 Journal Article, 2003 URL

Regulation of virulence gene expression in bacterial pathogens in, editor(s)E. A. Groisman , Principles of Bacterial Pathogenesis , Academic Press, 2001, pp75 - 132, [Dorman, C. J., Smith, S. G. J.] Book Chapter, 2001 DOI

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 ] Book Chapter, 2001

Burns LS, Smith SG & Dorman CJ , Interaction of the FimB integrase with the fimS invertible DNA element in Escherichia coli in vivo and in vitro, Journal of Bacteriology, 182, (10), 2000, p2953 - 2959 Journal Article, 2000 URL TARA - Full Text URL

Smith SG & Dorman CJ , Functional analysis of the FimE integrase of Escherichia coli K-12: isolation of mutant derivatives with altered DNA inversion preferences, Molecular Microbiology, 34, (5), 1999, p965 - 979 Journal Article, 1999 URL DOI

Porter ME, Smith SG & Dorman CJ , Two highly related regulatory proteins, Shigella flexneri VirF and enterotoxigenic Escherichia coli Rns, have common and distinct regulatory properties , FEMS Microbiol Lett, 162, (2), 1998, p303 - 309 Journal Article, 1998 DOI URL

Targeting and assembly of fimbriae in, editor(s)Phoenix, D.A. , Protein Targeting and Translocation, London, Portland Press, 1998, pp143 - 167, [Smyth, C.J., Smith, S.G.J. & Marron, M.B.] Book Chapter, 1998

Dove S, Smith SGJ, Dorman CJ, Control of Escherichia coli type 1 fimbrial expression in stationary phase: a negative role for RpoS, Molecular and General Genetics , 254, (1), 1997, p13 - 20 Journal Article, 1997

Control of type 1 fimbrial expression by a random genetic switch in Escherichia coli in, editor(s)M. McCrae, JR Saunders, CJ Smyth N Stow , Molecular Aspects of Host-Pathogen Interactions, Society for General Microbiology Symposium 55, 1997, pp191 - 210, [Dorman CJ, Nolan NC, Smith SGJ] Book Chapter, 1997

Smyth, C. J., Marron, M. B., Twohig, J. M. G. J. & Smith, S. G. J., Fimbrial adhesins: similarities and variations in structure and biogenesis, FEMS Immunology and Medical Microbiology, 16, 1996, p127 - 139 Journal Article, 1996

Fimbriae of Escherichia coli in, editor(s)Gyles, C.K. , Escherichia coli in Domestic Animals and Humans, Wallingford, U.K., CAB International, 1994, pp399 - 435, [Smyth, C. J., Marron, M. B. and Smith, S. G. J.] Book Chapter, 1994

C.J. Smyth, S.G.J. Smith, Expression of fimbriae in human enterotoxigenic Escherichia coli , Vaccine, 4, 1992, p288- Journal Article, 1992

Bacterial fimbriae: variation and regulatory mechanisms in, editor(s)C Hormaeche , Molecular biology of bacterial infections: Current status and future perspectives, Cambridge University Press, 1992, pp267 - 297, [Smyth CJ, Smith SGJ] Book Chapter, 1992

Non-Peer-Reviewed Publications

Microbial Recognition by Epithelium in, editor(s)David Proud , The Pulmonary Epithelium in Health and Disease, John Wiley & Sons, Ltd, 2008, pp169 - 185, [CM. Greene, S.G. J. Smith] Book Chapter, 2008

Dorman CJ, Stereotypic and stochastic issues in bacterial virulence gene expression, Eighth European Workshop Conference on Bacterial Protein Toxins, Kloster Banz, Germany, 1997 Invited Talk, 1997

Research Expertise

Description

My laboratory investigates how gram-negative bacteria, in particular E. coli and Salmonella, attach to and invade human cells. We are currently using Cellomics-based approaches to more accurately quantify bacterial invasion. This methodology also generates information on the kinetics of invasion and the cellular location of the invading bacteria. We are also interested in the gene regulatory mechanisms that govern attachment by E. coli e.g. the Rns virulence regulator.Invasion of cellular barriers by bacteria can be a prelude to entrance into the bloodstream. We are using transcriptomics to identify genes in E. coli that are regulated in response to human serum and its anti-bacterial components. More recently, and in collaboration with the Royal College of Surgeons in Ireland, we have shown that human estrogen can modulate the virulence of Pseudomonas aeruginosa.

Projects

  • 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.
  • Funding Agency
    • SFI
  • Date From
    • 1/10/10
  • Date To
    • 1/10/14
  • 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.
  • Funding Agency
    • HRB
  • Date From
    • 1/1/11
  • Date To
    • 1/6/14
  • 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.
  • Funding Agency
    • HRB
  • Date From
    • 1/1/11
  • Date To
    • 1/6/14

Keywords

Antibiotics; Biological Markers; Brain; Cell Communication; Diagnostics; Digestive System; DNA; E.coli; Eschericia coli; Extracellular Matrix; Gastrointestinal Diseases/Disorders; Gene Expression; Gene Regulation; Genetically Modified Organisms; Genomes, Genomics; Infectious Diseases; Infectious Diseases/Agents; Meningitis; Microbial Biotechnology, Microbial Modelling; Molecular Biology; Molecular Genetics; Nucleic Acids; Pathogenesis; Proteins and Macromolecules; Proteomics; Recombinant DNA; Respiratory System; Salmonella; Urogenital System

Recognition

Memberships

Member Society for General Microbiology UK

Member American Society for Microbiology