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Dr. Stephen Smith

Associate Professor (Clinical Microbiology)
The Senior Tutor (Senior Tutor)
      
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Dr. Stephen Smith

Associate Professor (Clinical Microbiology)

 Steve.Smith@tcd.ie

 

The Senior Tutor (Senior Tutor)


  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
Project Title
 High throughput analysis of enterobacterial invasion
From
1/10/10
To
1/10/14
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
Project Title
 E. coli sepsis; better treatment options using genomics
From
1/1/11
To
1/6/14
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
Project Title
 E. coli sepsis; better treatment options using genomics
From
1/1/11
To
1/6/14
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

Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
French Basic Basic Basic
Details Date From Date To
Member Society for General Microbiology UK
Member American Society for Microbiology
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, 2021, Oral Presentation, PUBLISHED
Stephen Smith, RISE"ing to the occasion on a shoestring. Technology-enhanced Microbiology practical teaching., Microbiology Society Annual Conference erence, Online , April 2021, 2021, Oral Presentation, PUBLISHED
Naoise McGarry, Stephen Smith, Escherichia coli serum resistance : roles for cell number and Haemolysin., Microbiology Society Annual Conference, Edinburgh , April , 2020, Microbiology Society , Invited Talk, PUBLISHED
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 Society , Invited Talk, PUBLISHED
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 Society , Invited Talk, PUBLISHED
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 - 102, Journal Article, PUBLISHED  URL
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 - 20, Journal Article, PUBLISHED  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), 2019, Poster, PUBLISHED  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, 2019, Poster, PUBLISHED  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, 2019, Poster, PUBLISHED  URL
  

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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, PUBLISHED
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, PRESENTED
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 Society, Meeting Abstract, PUBLISHED

  


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.