Dr. Stephen Smith

Dr. Stephen Smith

Associate Professor, Clinical Microbiology

The Senior Tutor, Senior Tutor

3531896 8590http://www.medicine.tcd.ie/clinical_microbiology/research/smith.php

Publications and Further Research Outputs

  • 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 - 12Journal Article, 2016, URL
  • 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, p71-79Journal Article, 2016, URL
  • Pares S, Smith SG, Functional Analysis of the PagN protein of Salmonella enterica , American Society for Microbiology, Boston, 16/05/2014, 2014Poster, 2014
  • 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 - 10Journal 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 - 4Journal Article, 2016, DOI , URL , TARA - Full Text
  • Marassi, Valentina and Di Cristo, Luisana and Smith, Stephen G J and Ortelli, Simona and Blosi, Magda and Costa, Anna L and Reschiglian, Pierluigi and Volkov, Yuri and Prina-Mello, Adriele, Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents, Royal Society open science, 5, (1), 2018, p171113Journal Article, 2018, DOI , URL , TARA - Full Text
  • , Inhibition of Vascular Endothelial Cell Leak Following Escherichia coli Attachment in an Experimental Model of Sepsis, Critical care medicine, 2018Journal Article, 2018
  • Molloy K1, Smith SG, Cagney G Dillon ET, Greene CM, McElvaney NG., Characterisation of the Major Extracellular Proteases of Stenotrophomonas maltophilia and Their Effects on Pulmonary Antiprotease, Pathogens, 8, (3), 2019, p1 - 20Journal Article, 2019, URL
  • McKiernan PJ, Smith SGJ, Durham AL, Adcock IM, McElvaney NG, Greene CM., The Estrogen-Induced miR-19 Downregulates Secretory Leucoprotease Inhibitor Expression in Monocytes., Journal of Innate Immunity, 12, 2020, p90 - 102Journal Article, 2020, URL
  • Sinead Moynihan, Stephen Smith, The O6 antigen of Escherichia coli strain CFT073 is a target for Myoviridae, Access Microbiology, Microbiology Society AC19, Belfast UK, 08 April 2019, 1, (1a), 2019Poster, 2019, URL
  • Naoise McGarry, Stephen Smith, Characterisation of rpoS alleles in UPEC strain CFT073, ACCESS MICROBIOLOGY, Microbiology Society AC19, Belfast UK, 8-4-19, 1, (1a), Microbiology Society, 2019Poster, 2019, URL
  • Aileen Hartnett, Stephen Smith, Susan Knowles, A micro luminescence-based assay to measure serum susceptibility in Escherichia coli , Access Microbiology, Microbiology Society AC19, Belfast UK, 08 April 2019, 1, (1a), Microbiology Society, 2019Poster, 2019, URL
  • Naoise McGarry, Stephen Smith, Escherichia coli serum resistance : roles for cell number and Haemolysin., Microbiology Society Annual Conference, Edinburgh , April , 2020, Microbiology SocietyInvited Talk, 2020
  • Aileen Hartnett, Susan Knowles, Sara Lydon, Stephen Smith, Phenotypic and genotypic characterization of Escherichia coli associated neonatal sepsis in Ireland, Microbiology Society Annual Conference , Edinburgh , April , 2020, Microbiology SocietyInvited Talk, 2020
  • Sinead Moynihan, Emma Pearson, Jerome Fennell, Stephen Smith, Extracellular polymers contributing to biofilm formation in Klebsiella pneumoniae, Microbiology Society Annual Conference , Edinburgh , April , 2020, Microbiology SocietyInvited Talk, 2020
  • Naoise McGarry, Stephen Smith, The extracellular glycome of extra-intestinal pathogenic Escherichia coli and its role in serum resistance, Microbiology Society Annual Conference , April 2021, 2021Oral Presentation, 2021
  • Stephen Smith, RISE"ing to the occasion on a shoestring. Technology-enhanced Microbiology practical teaching., Microbiology Society Annual Conference erence, Online , April 2021, 2021Oral Presentation, 2021
  • 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 - 1646Journal 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 - 937Journal Article, 2003, 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 ]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 - 2959Journal Article, 2000, URL , TARA - Full Text
  • 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 - 979Journal Article, 1999, DOI , URL
  • 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 - 309Journal Article, 1998, DOI , URL
  • 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 - 139Journal Article, 1996
  • 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
  • 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
  • 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
  • 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 - 20Journal Article, 1997, DOI , URL
  • Regulation of virulence gene expression in bacterial pathogens in, E. A. Groisman , Principles of Bacterial Pathogenesis , Academic Press, 2001, pp75 - 132, [Dorman, C. J., Smith, S. G. J.]Book Chapter, 2001, DOI , URL
  • 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 - 5363Journal Article, 2006, DOI , TARA - Full Text
  • 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 - 255Journal 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 - 11Journal Article, 2007
  • 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 - 2109Journal 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 - 2209Journal 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 - 1142Journal Article, 2008
  • Lambert MA, Smith SG, The PagN protein of Salmonella enterica serovar Typhimurium is an adhesin and invasin. , BMC Microbiol, 8, 2008, p142 - 142Journal Article, 2008
  • Lambert MA, Smith SG., The PagN protein mediates invasion via interaction with proteoglycan., FEMS Microbiol Lett., 2009, p209 - 216Journal Article, 2009
  • 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 - 1652Journal 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 - 1114Journal Article, 2010
  • 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), 2010Journal Article, 2010, TARA - Full Text
  • 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 - 2806Journal 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 - 5831Journal Article, 2010, DOI , URL , TARA - Full Text
  • Rowe SE, Mahon V, Smith SG, O'Gara JP, A novel role for SarX in Staphylococcus epidermidis biofilm regulation, Microbiology, 157, (4), 2011, p1042 - 1049Journal Article, 2011
  • 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 - 1986Journal Article, 2012
  • Vivienne Mahon, Robert P. Fagan, Stephen G.J. Smith, Snap denaturation reveals dimerization by AraC-like protein Rn, Biochimie, 94, 2012, p2058 - 2061Journal Article, 2012
  • 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, pe71Journal Article, 2013, TARA - Full Text
  • 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 - 205Journal Article, 2014, TARA - Full Text
  • Miajlovic H, Smith SG., Bacterial self-defence: how Escherichia coli evades serum killing., FEMS Microbiol Lett., 354, 2014, p1 - 9Journal Article, 2014, TARA - Full Text
  • 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
  • 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 - 454Journal Article, 2011
  • 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
  • Karen Jordan, Meadhbh Hunt, Stephen G. Smith., New options for the treatment of Escherichia coli ST131 infections defined by bioluminometry, ANTIMICROBIAL RESISTANCE AND ONE HEALTH, NUIM, Ireland, 29/8/17, Microbiology SocietyMeeting Abstract
  • 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
  • Dorman CJ, Stereotypic and stochastic issues in bacterial virulence gene expression, Eighth European Workshop Conference on Bacterial Protein Toxins, Kloster Banz, Germany, 1997Invited Talk

Research Expertise

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.

  • 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
    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

Recognition

  • Member Society for General Microbiology UK
  • Member American Society for Microbiology