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Research

The Discipline of Clinical Microbiology has research facilities at Sir Patrick Duns Research Laboratory and the Trinity Centre Tallaght

Current Research Projects

Invasive fungal infections

Professor Rogers’ research has focused on developing improved diagnostics for invasive aspergillosis particularly in the setting of treatment for haematological malignancies. Previous work showed that by combining immunological and molecular tests, the diagnostic performance of fungal biomarkers could be optimised (Rogers TR et al British Journal of Haematology 161: 517-24; 2013). There is ongoing collaboration with other European research groups in this area through our participation in the Fungal PCR Initiative (FPCRI). More recent work has been focused on the epidemiology of multi-triazole drug resistance in Aspergillus fumigatus and we were the first to report this in Ireland (Dunne K et al Clinical Infectious Diseases 65:147-9; 2017). This work continues through collaborations with researchers at Imperial College London and University of Nijmegen, Netherlands. We have published a small series of post-influenzal aspergillosis due to multi-triazole resistant A. fumigatus (Talento A et al Mycoses E Pub 2018) and continue with work investigating the  association between influenza and aspergillosis. A related project is investigating the prevalence of A. fumigatus colonization/infection in patients with Chronic Obstructive Pulmonary Disease (COPD)

Research team:
Dr Katie Dunne, Post-Doctoral Researcher
Dr Alida Talento, Adjunct Clinical Assistant Professor
Dr Sarmad Waqas, Clinical Lecturer

Collaborators:
Prof Juergen Loeffler, University of Wuerzburg, Germany
Prof Mat Fisher, Dr Darius Armstrong-James, Imperial College London, UK
Prof Jacques Meis, University of Nijmegen, The Netherlands

Funding (previous and current):
EU Framework 7
Gilead Sciences

Mycobacterial infections

Next generation sequencing (NGS) is being applied to the investigation of Mycobacterium tuberculosis, with a view to improving the speed to detection of M. tb in clinical specimens and identifying antibiotic resistance-associated gene mutations (Pankhurst LJ et al Lancet Respiratory Medicine 4: 49-58; 2016). This work has involved collaboration with colleagues in University of Oxford and research conducted in collaboration with the Irish Mycobacteria Reference Laboratory (IMRL) which characterised, for the first time,  the genomics of multi-drug resistant M. tb in Ireland (Roycroft E et al, Journal Of Infection 76:55-67; 2017).
We have recently participated in  a national incident investigation of serious Mycobacterium chimaera infections complicating open heart surgery. Together with the IMRL, we have performed NGS on both clinical and environmental isolates of M. chimaera which has provided new insight into its epidemiology. We were the first group to publish the genome sequence of M. chimaera (Mac Aogáin M et al, Genome Announcements 3: pii: e01409-15. doi: 10.1128/genomeA.01409-15
2015) . We are currently studying the clinical features of respiratory M. chimaera infections matched to their genome sequences to look for any associations.

Research team:
Dr M Fitzgibbon, Chief Medical Scientist, IMRL
Dr Emma Roycroft, Specialist Medical Scientist, IMRL
Ms Simone Mok, PhD student

Collaborators:
Prof Derrick Crook, University of Oxford
Irish Mycobacteria Reference Laboratory
Prof Joe Keane, Dr Anne Marie Mc Loughlin, St James’s Hospital

Funding:
Department of Clinical Microbiology, TCD
Health Services Executive

Nosocomial infections

The current focus is on improving understanding of Clostridium difficile infections (CDI) in hospitalised patients. We are currently analysing the results of a hospital-wide study we recently completed using NGS of C. difficile isolates to improve understanding of the frequency of nosocomial transmission events.  Related research has investigated recurrent C. difficile cases to understand how often this is due to the same or newly acquired strains (Mac Aogáin et al. Journal of Hospital Infection 90:108-116; 2015). We are also investigating the intestinal microbiome of cases of recurrent CDI with the aim of identifying associated changes in the make-up of the microbiome. The final strand to this theme involves investigation of animal C. difficile infections to see if there is a link with human infections.

Research team:
Dr Micheal Mac Aogáin, Post-DoctoralResearch Fellow
Dr Geraldine Moloney, Clinical Research Fellow, PhD student

Collaborators:
Prof Derrick Crook, University of Oxford
Dr Máire Mac Elroy, Senior Research Officer, Central Veterinary Research Laboratory, Backweston

Funding:
Health Research Board
Irish Research Council

Escherichia coli genomics, immune evasion and cellular invasion

Professor SmithProfessor Smith's research is focused on gram-negative Enterobacteria, in particular Escherichia coli.
Using molecular & cell biology, in conjunction with genomics we are characterising extraintestinal pathogenic E. coli  (ExPEC) that infects the human body outside the intestinal tract.  The mechanisms by which these bacteria cross mammalian cell membranes is a long standing interest and  we use high throughput microscopy in collaboration with Jez Simpson UCD to characterise this (see fig 1 below). 
The genomics and transcriptome of ExPEC is also being actively investigated. The genomes of ExPEC from adults and neonates are being sequenced. The  transcriptomic response of ExPEC to antibacterial assaults is being characterised by RNAseq and other methods (see fig 2).  We hope to build up a picture of what makes ExPEC such a devastating pathogen in the human bloodstream.

Current team
3 x graduate students

Funders  National Children’s Research Centre

Past Funders
Health Research Board
Science Foundation Ireland
Enterprise Ireland

Other research interests
The role of OmpA in E. coli infection
Antibiotic resistance in GNBs and new drugs
miRNA in infection

Collaborators
Prof Catherine Greene RCSI
Prof Steve Kerrigan RCSI
Prof Jez Simpson UCD
Prof Adrielle Prino Mella TCD

 


Fig 1  Interaction of Hek + E. coli with mammalian cells. Invasive bacteria green, external bacteria orange, human nuclei blue.


Fig 2 RNAseq to identify the genes induced by the innate immune system.

AIM CF (Airway Microbiome in Cystic Fibrosis)

 
PI: Dr Julie Renwick

AIM CF is a branch of the larger Study of Host Immunity and Early Lung Disease in Cystic Fibrosis (SHIELD CF) biobanking project established by Prof Paul McNally (RCSI) and Dr Barry Linnane (LUH). The AIM CF project aims to characterise the lower airway microbiome of children with CF from birth. We have employed a 16S rRNA microarray, 454 pyrosequencing, Illumina MiSeq and NovaSeq to characterise the upper and lower CF airway microbiome and compare it to healthy controls. This is an ongoing longitudinal study and we are now beginning to focus on characterising the metabolic profiles of these microbial communities with the specific goal of identifying bacterial metabolites with the potential to influence inflammation and thus disease severity in CF.

 

 

 

Recent publications & presentations:

  1. Julie Renwick, Jenny Lennon, Rebecca Reilly, Philip Murphy, Orla O'Sullivan, Paul Cotter, Barry Linnane, Paul G McNally. (2017). Temporal Evolution Of The Lower Airway Microbial Community In Preschool Children With CF. Pediatric Pulmonology. 52; S194-S195.
  2. Emma Reece, Siobhán McClean, PC Greally, Julie Renwick (2017). A short-term longitudinal study of the paediatric cystic fibrosis airway microbiome. J. Cyst. Fibr. (16) S109.
  3. Julie Renwick, Paul McNally, Bettina John, Todd DeSantis, Barry Linnane, and Philip Murphy. (2014). The Microbial Community of The Cystic Fibrosis Airway is Disrupted in Early Life. PLoS ONE. 19;9(12): e109798.

Staff/ students: Gillian McDermott (MSc student)

Funded by:      

SPIN CF (Study of Polymicrobial INteractions in CF)

PI/s: Dr Julie Renwick & Dr Peter Greally
This project focuses on exploring polymicrobial interactions between common CF pathogens and the impact of these interactions on the CF airway disease. This research aims to determine which microorganisms interact in the CF airway and how these interactions may impact on inflammation and disease progression. It is our vision that our work will pave the way for specific tailored therapies for airway infections in patients with CF. 

Recent publications/ presentations:

  1. Reece E., Doyle S., Greally P.,Renwick J and McClean S. (2018). Aspergillus fumigatus inhibits Pseudomonas aeruginosa in co-culture: Implications of a mutually antagonistic relationship on virulence and inflammation in the CF airway. Front. Microbiol. (9) 1205.
  2. E Reece, S Doyle, J Renwick, P Greally, S Mc Clean. (2018) Mutual antagonism: a complex coexistence of Aspergillus fumigatus and Pseudomonas aeruginosa in the cystic fibrosis airway. J. Cys. Fibr. (17) S44-S45. Published abstract.
  3. Reece E., Segurado R., Jackson A., McClean S., Renwick J.* and Greally P. (2017) Co-colonisation of the airways with A. fumigatus and P. aeruginosa is associated with poorer health in patients with CF: An Irish registry analysis. BMC Pulmonary Medicine. Apr 21;17(1):70. doi: 10.1186/s12890-017-0416-4.

Staff/ students: Dr Emma Reece (Post-doctoral scientist)

Funded by:

ACRE (Antimicrobial Coating pRojEct)


PI/s: Dr Julie Renwick & Dr Jerome Fennell



Antimicrobial Resistance (AMR) is a serious global health concern with estimates of >10 billion AMR related deaths world wide by 2050. Contaminated surfaces contribute to transmission of hospital pathogens and AMR superbugs. This project aims to incorporating a new antimicrobial technology into the hospital setting and to assess its ability to reduce bacterial bioburden and thus prevalence of resistant superbugs such as CPE in the hospital environment. This is a collaborative project lead by scientists and clinicians in Kastus, Elda Biotech, Trinity College and Tallaght University Hospital.
Funded by:      

Molecular Characterisation of Neisseria gonorrhoeae using Whole Genome Sequencing

Molecular Characterisation of Neisseria gonorrhoeae using Whole Genome Sequencing – collaboration with Professor Magnus Unemo in WHO Gonococcal Reference Laboratory, Orebro, Sweden.

Past Projects

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.

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

Samonella

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.

 

Collaborative Institutes

  • The Institute of Technology Tallaght (ITT). We have a long standing collaborative relationship with Dr. Maire Callaghan and Dr. Emma Caraher in the Centre for Microbial Host Interactions (CMHI) in ITT and Dr. Bernie Creaven in the Chemistry department.  
  • The Royal College of Surgeons (RCSI), Beaumont hospital, Dublin. 
  • The National Children's Research Centre, Our Lady’s Children's hospital Crumlin. In particular with the Study of Host Immunity and Early Lung Disease (SHEILD CF) established by Dr Paul McNally and Dr Barry Linnane. 
  • Panum Instituttet, University of Copenhagen.
  • Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
  • Nanyang Technology University, Lee Kong Chian School of Medicine, Singapore. Prof Sanjay Chotirmall.
  • University College Dublin (UCD),  School of Biomolecular and Biomedical Science. Dr Siobhan McClean
  • Elda Biotech. Dr Elaine Kenny
  • Kastus. Dr James Kennedy & Dr Brendan Duffy.
  • Teagasc, Moorepark Technology Centre, Fermoy, Cork. Dr Paul Cotter & Dr Orla O’Sullivan