Consultant in Medical Microbiology & Clinical Professor Trinity College

Department of Clinical Microbiology, Trinity College,
Adelaide and Meath hospital inc. the National Children's Hospital,
Tallaght,
Dublin 24.

Email: Philip.murphy@amnch.ie

My research focuses on the epidemiology and pathogenesis of chronic lung disease (CLD) pathogens, in particular Cystic Fibrosis (CF) airway pathogens. Our research is translational in the sense of bridging fundamental data to clinical care. I am currently involved in many projects in this area. We are focused on investigating bacterial adaptations during biofilm formation within the CF lung that lead to bacterial persistence and antimicrobial resistance. Another project we have recently embarked on aims to establish the connection between the microbiome in the CF airways and lung disease progression.

 

RESEARCH PROJECTS

Polymicrobial Communities in the Lower Airways of Infants and Children with Cystic Fibrosis
The CF lung has recently been shown to harbour many bacterial species at any one time. Many of these bacteria have never before been associated with the CF airways.  We are investigating the microbial community in the lungs of infants and children with CF using advanced microarray technologies to determine the ability of the entire microbial community to influence early CF lung disease.

 

Circular Phylogenetic tree comparing changes in taxa abundance between non-CF and CF lower airways.
Heatmap represents the change taxa abundance relative to the mean change in the non-CF BAL group (inner rings).

 

 

 

 

 

 

 

 

Aspergillus fumigatus Infection in CLD
A. fumigatus is the most commonly isolated fungal pathogen in CF. It mainly causes Allergic Bronchopulmonary Aspergillosis (ABPA) in these patients. We are interested in determining the underlying factors that make a CLD patient more or less susceptible to A. fumigatus infection. We have developed molecular techniques for detecting and enumerating A. fumigatus in various clinical samples and are now investigating the level of antifungal drug resistance among our collection of genotyped A. fumigatus isolates.

Pseudomonas aeruginosa anti-biofilm therapies
P. aeruginosa is the most common microbial complication in CF and it is almost impossible to eradicate in CF patients once infection has been established. This bacterium and many other CF pathogens can form highly drug resistant biofilms during infection. Our research group is focused on finding novel ways of disrupting biofilm growth. We are currently testing the anti-biofilm properties of novel compounds using advanced flow cell technologies in the Panum Institute, Copenhagen.

Epidemiology and pathogenesis of novel and emerging pathogens in CF
Our laboratory is also the National CF Microbiology reference laboratory and clinical services include Burkholderia cepacia complex molecular characterisation, P. aeruginosa clonal analysis of the epidemiologically related bacteria from people with CF and identification of novel CF bacteria. We are currently investigating the pathogenicity of two novel CF bacteria employing tissue culture assays and in vivo testing using the Galleria mellonella infection model. 

 

                 

Herbaspirillum spp detected in an Irish CF clinic.
A) Clone analysis of RAPD profiles from Herbaspirillum spp detected in CF patients suggest a common source of infection or transmissibility. B) Herbaspirillum is capable of causing infection and death in our G. mellonella insect model.

CURRENT STAFF AND STUDENTS
Dr Julie Renwick BSc, PhD, PGHDE
Post-doctoral research fellow & research group coordinator
Mr Jonathan Collins BSc
Researcher and manager of the CF reference laboratory
Ms Priya Kapoor BSc
PhD student
Ms Katie Dunne BSc, GradCertBiomedSc
PhD student

FUNDING BODIES
The Cystic Fibrosis Association of Ireland (CFAI)
The National Children's Hospital (NCH)
Trinity College Dublin
The National Children's Research Centre (NCRC)

COLLABORATIVE INSTITUTES
The Institute of Technology Tallaght (ITT). We have a long standing collaborative relationship with Dr. Siobhan McClean, 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.
Second Genome, San Francisco, California.
Panum Instituttet, University of Copenhagen.
Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

REPRESENTATIVE PUBLICATIONS

• McNally P, Coughlan C, Bergsson G, Doyle M, Taggart C, Adorini L, Uskokovic MR, El-Nazir B, Murphy P, Greally P, Greene CM, McElvaney NG. 2011. Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis. J. Cyst. Fibros. Dec; 10(6):428-34. (PMID: 21784717)

• Bergsson, G., Reeves, E.P., McNally, P., Chotirmall S.H., Greene, C., Greally, P., Murphy, P., O’Neill, S.J. and McElvaney N.G. LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline. 2009.The Journal of Immunology. 183:543-551. (PMID: 19542465)

• Kelly S, Collins J, Maguire M, Gowing C, Flanagan M, Donnelly M, Murphy PG. An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit. J Antimicrob Chemother. 2008 Apr;61(4):901-7. (PMID: 18272512)

• Emma Caraher, Jonathan Collins, Gillian Herbert, Philip G. Murphy, Charles G. Gallagher, Mary J. Crowe, Máire Callaghan and Siobhán McClean. Evaluation of in vitro virulence characteristics of the genus Pandoraea in lung epithelial cells. 2008. J Med Microbiol. 57; 15-20. (PMID: 18065662)

• McManus, B. A., Coleman, D. C., Moran, G., Pinjon, E., Diogo, D., Bougnoux, M.-E., Borecka-Melkusova, S., Bujdakova, H., Murphy, P., d'Enfert, C., Sullivan, D. J. Multilocus sequence typing reveals that the population structure of Candida dubliniensis is significantly less divergent than that of Candida albicans. 2008. J Clin Microbiol. 46: 652-664. (PMID: 18057125)

More publications:

• Emma M. Caraher, Kiranmai Gumulapurapu, Clifford C. Taggart, Philip Murphy, Siobhán McClean, and Máire Callaghan. The effect of recombinant human lactoferrin on growth and the antibiotic susceptibility of the cystic fibrosis pathogen Burkholderia cepacia complex when cultured planktonically or as biofilms. J. Antimicrob. Chemother. 2007. 60: 546-554 (PMID: 17595284)

• E. Caraher & G. Reynolds & P. Murphy & S. McClean & M. Callaghan. Comparison of antibiotic susceptibility of Burkholderia cepacia complex organisms when grown planktonically or as biofilm in vitro.  Eur J Clin Microbiol Infect Dis. 2007. Vol 26, No 3, Pages 213-216.  (PMID: 17265071)

• Emma Caraher, Caroline Duff, Tracy Mullen, Suzanne Mc Keon, Philip Murphy, Máire Callaghan, Siobhán McClean.  Invasion and biofilm formation of Burkholderia dolosa is comparable with Burkholderia cenocepacia and Burkholderia multivorans. 2007. Journal of Cystic Fibrosis. 6; 49–56 (PMID: 16781896)

• Mullen, T, Markey K, Murphy P, McClean S, Callaghan M. Role of lipase in Burkholderia cepacia complex (Bcc) invasion of lung epithelial cells. 2007. Eur J Clin Microbiol Infect Dis. 15; 17874328. (PMID: 17874328)

• Gillow C, Shaw A, Moore JE, Elborn JS, Murphy PG. Antibiotic resistance and identification of uncommon Gram-negative bacteria isolated from sputum of adult patients with cystic fibrosis. British Journal of Biomedical Science. 2006. 63: 22-24. (PMID: 16613138)

• Duff C, Murphy PG, Callaghan M, McClean S.  Differences in invasion and translocation of Burkholderia cepacia complex species in polarised lung epithelial cells in vitro.  Microb Pathog. 2006 Oct-Nov. 41(4-5):183-92. (PMID: 16938423)