'FROM DISCOVERY TO RECOVERY'
Professor Sheila Patrick
Chair of Molecular Medical Bacteriology
1977 BSc (Honours Microbiology); University of Edinburgh
1981 PhD Microbiology; University of Edinburgh
2006 DSc Opportunistic pathogens of the normal human microbiota; University of Edinburgh
Fellow of the the Higher Education Academy
Chair, Society for Anaerobic Microbiology http://clostridia.net/SAM/
Opportunistic bacterial infections that arise from the normal resident human microbiota, with emphasis on anaerobic bacteria.
The aim of Professor Patrick’s research is to contribute to our understanding of opportunistic bacterial infection so that we can better understand these diseases and improve on prevention, diagnosis and treatment.
Professor Patrick has nearly 30 years experience of studying the obligately anaerobic bacterium Bacteroides fragilis. B. fragilis is a member of the normal resident human intestinal microbiota and an important opportunistic pathogen capable of causing considerable morbidity and mortality. Professor Patrick is Principal Investigator on the Wellcome Trust Sanger Institute UK B. fragilis whole genome sequencing project (http://www.sciencemag.org/cgi/content/full/307/5714/1463: http://www.sanger.ac.uk/Projects/B_fragilis/).
This has generated exciting data in relation to our understanding of the mechanisms that generate the heterogeneity of surface component expression, which she first reported in the 1980s. These mechanisms involve DNA recombination events at an extensive number of loci in a variety and number that have not been observed, to date, in other bacteria.
Since the mid 1990s her studies of biofilm associated prosthetic joint infection in artificial hip failure have highlighted the importance the anaerobe, Propionibacterium acnes. P. acnes, predominantly colonises human skin and is also implicated in a variety of inflammatory conditions including acne. In 2004 Professor Patrick was invited to present her studies at the Association of Bone and Joint Surgeons Carl T Brighton Annual Workshop on Musculoskeletal Infection, Tampa, Florida. This has resulted in the adoption of her techniques in the USA. Her studies have resulted in a re-assessment of the phylogeny of this group of bacteria and the discovery of variable expression of putative virulence determinants amongst the different groups.
Professor Patrick’s research has generated considerable global interest and resulted in collaborations in Africa, USA, Europe, Australia and South America.
Mechanisms of virulence of Bacteroides fragilis (Department of Education and Learning NI funded)
The data generated by the complete genome sequencing project (Cerdeño-Tárraga AM, Patrick S et al 2005 Science 307, 1463-1465) is being exploited in relation to putative virulence determinants. Selected genes, identified in silico in the B. fragilis genome sequences, are being studied in relation to their potential involvement in virulence and host colonisation. The effects of allelic replacement gene knockouts on phenotype, in collaboration with Dr Garry Blakely University of Edinburgh, are being examined.
Propionibacterium acnes as an important risk factor for prostate cancer (Prostate Cancer Charity UK funded)
Recent studies, including collaboration between Dr Andrew McDowell (project PI and Senior Post-doctoral Researcher in Professor Patrick’s laboratory) and laboratories in Australia and Sweden, have provided evidence that Propionibacterium acnes infects the human prostate gland where it is associated with acute and chronic inflammatory changes that could potentially lead to cancer development. This discovery may represent a breakthrough in our understanding of the complex origins of this common cancer and highlight new treatments. Currently, studies to confirm P. acnes infection in prostate cancer tissue from patients in Northern Ireland, as well as in vitro studies to determine the interaction between different phylogenetic types of P. acnes with human tissue culture cell lines in relation to key inflammatory mediators (in collaboration with Dr Lorraine Martin, Pharmacy QUB) that are important in carcinogenesis, are ongoing.
Skin bacteria as a source of surgical infections: molecular epidemiology and prevention of wound contamination (NI Health & Social Care R & D Office funded)
A recent study of spinal surgery, carried out in Professor Patrick’s Laboratory showed that nearly 30% of operative wounds contained bacteria of the normal skin microbiota, despite pre-operative treatment of the patient’s skin with the antiseptic povidone-iodine (PVI); however, as peroperative antibiotic prophylaxis was successful, these patients did not have post-surgical infection. The rise in antibiotic resistance, typified by meticillin resistant Staphylococcus aureus (MRSA), will inevitably result in an increase in life threatening post-operative wound infection, potentially to the 30% level of wound contamination observed in this study. It is therefore proposed to pre-empt such a scenario by addressing the current procedures for skin antisepsis prior to surgery. Chlorhexidine gluconate (CHG) and PVI are skin disinfection antiseptics with different modes of bacterial killing; however, there have been no randomised controlled trials to determine if CHG used in addition to PVI reduces wound contamination in the operative setting. The effect of the sequential pre-operative treatment of patient skin with antiseptic CHG and PVI, on surgical wound contamination in a randomised controlled trial of patients undergoing surgery at Musgrave Park Hospital Belfast is ongoing. This study will enable us to determine if by using both CHG and PVI it will be possible to counter the potential rise in post-operative infection arising from antibiotic resistant bacteria.
RESEARCH STAFF AND STUDENTS
Dr Andrew McDowell (Senior post-doctoral Research Fellow), Dr Emma Barnard (Post-doctoral Research Assistant), Dr Andrew Lee (Post-doctoral Research Assistant) Ms Una Martin (Research Nurse), Mr Danny O’Connor (Post-graduate Student), Mr Darragh McCafferty (Post-graduate Student)
BOOK AND BOOK CHAPTER PUBLICATION
Patrick S, Larkin MJ 1995. Immunological and molecular aspects of bacterial virulence. Chichester; J. Wiley. 275pp
Patrick, S. 2002. Bacteroides. Chapter 91, pp 1921-1948. In: Molecular Medical Microbiology B Boulnois, G Griffin, C Hormaeche, G Keusch, M Levine, H Smith, P Williams, M Sussman (Eds). London: Academic Press.
Patrick S and Duerden BI. 2006. Gram-negative non-spore forming obligate anaerobes. Chapter 45, pp 541-556. In: Principles and Practice of Clinical Bacteriology 2nd Edn. SH Gillespie, P Hawkey (Eds). London: Wiley.
Patrick S and McDowell A The Propionibacteriaceae. In: Volume 5 Bergey's Manual of Systematic Bacteriology 2nd Edn. H-J Busse, M Goodfellow, P Kämpfer, W Ludwig, JT Staley, K Suzuki, WB Whitman (Eds). New York: Springer-Verlag. In press. http://www.bergeys.org/
McDowell A and Patrick S. 2011. Propionibacterium Chapter 13 In: Molecular detection of human bacterial pathogens. D Liu (Ed). Boca Raton, Florida: Taylor & Francis Group.