Room 447. Lab 339 Lab ext. 2080
Research interests
E-mail: pwotoole@ucc.ie
Tel +353-21-4903997
Fax +353-21-4903101
- 1984 BA (Mod), Microbiology, Trinity College Dublin
- 1987 PhD Microbial Genetics, Trinity College Dublin
- 1988-1992 Post-doctoral Fellow, University of Lund, Sweden
- 1992-1995 Research Associate, University of Victoria, British Columbia, Canada
- 1995-2002 Lecturer in Microbiology, Institute of Molecular BioSciences, Massey University New Zealand
- 2002- present, Lecturer, Molecular Genetics, Department of Microbiology, University College Cork
Selected Recent Publications
Recent Lactic acid bacterium papers
Corr, S.C., Li, Y., Riedel., C.U., O'Toole, P.W., Gahan, C.G.M., and Hill, C. 2007. Bacteriocin production as a mechanism for the anti-infective activity of Lactobacillus salivarius UCC118. Proc. Nat. Acad. Sci. USA, 104: 7617-7621. [Cover article].
Claesson, M.J., van Sinderen, D., and P.W. O'Toole. 2007. The genus Lactobacillus - a genomic basis for understanding its diversity. FEMS Microbiol. Letts, 269: 22-28.
Canchaya, C., M. J. Claesson, G. J. Fitzgerald, D. van Sinderen and P. W. O'Toole. 2006. Diversity of the genus Lactobacillus revealed by comparative genomics of five species. Microbiol. 152: 3185-3196.
Li, Y., E. Raftis, C. Canchaya, G. F. Fitzgerald, D. van Sinderen and P. W. O'Toole. 2006. Polyphasic analysis indicates that Lactobacillus salivarius subsp. salivarius and Lactobacillus salivarius subsp. salicinius do not merit separate subspecies status. Int. J. Sys. Evol. Microbiol. 56: 2397-2403.
Claesson, M. J., Y. Li, S. Leahy, C. Canchaya, J.-P. van Pijkeren, A. M. Cerdeno-Tárraga, J. Parkhill, S. Flynn, G. C. O'Sullivan, J. K. Collins, D. Higgins, F. Shanahan, G. F. Fitzgerald, D. van Sinderen, and P. W. O'Toole. 2006. Multireplicon genome architecture of Lactobacillus salivarius. Proc. Nat. Acad. Sci. U.S.A. 103: 6718-6723 [Cover article].
Ventura, M., C. Canchaya, E. Altermann, R. Barrangou, C. D. Walker, R. Zink, J. Steele, J. Broadbent, T. R. Klaenhammer, G. F. Fitzgerald, P. W. O'Toole, and D. van Sinderen. 2006. Genomics and transcriptional analysis of prophages identified in the genomes of Lactobacillus gasseri, Lactobacillus salivarius and Lactobacillus casei. Appl. Env. Microbiol. 72: 3130-3146
van Pijkeren, J.-P., C. Canchaya, K. A. Ryan, Y. Li, M. Claesson, B. Sheil, L. Steidler, L. O'Mahony, G. F. Fitzgerald, D. van Sinderen, and P. W. O'Toole. 2006. Genome-wide identification of surface proteins in the probiotic bacterium Lactobacillus salivarius UCC118, and functional characterization of sortase-dependent proteins. App. Env. Microbiol. 72: 4143-4153..
Rakonjac, J., P. W. O'Toole, and M. Lubbers. 2005. Isolation of lactococcal prolate phage-phage recombinants by an enrichment strategy reveals two novel host range determinants. J Bacteriol 187:3110-21.
Schiemann, A. H., J. Rakonjac, M. Callanan, J. Gordon, K. Polzin, M. W. Lubbers, and P. W. O'Toole. 2004. Essentiality of the early transcript in the replication origin of the lactococcal prolate phage c2. J. Bacteriol. 186:8010-7.
Rakonjac, J., L. J. Ward, A. H. Schiemann, P. P. Gardner, M. W. Lubbers, and P. W. O'Toole. 2003. Sequence diversity and functional conservation of the origin of replication in lactococcal prolate phages. Appl Environ Microbiol 69:5104-14.
Recent Helicobacter publications
Snelling, W.J., Moran, A.P., Ryan, K.A., Scully, P., McGourty, K., Cooney, J.C, Annuk, H. and P. W. O'Toole. 2007. HorB (HP0127) is a gastric epithelial cell adhesin. 2007. Helicobacter 12: 200-209.
Waters, R.C., P.W. O'Toole, and K.A. Ryan. 2007. The FliK Protein and Flagellar Hook-Length Control. Protein Science 16: 769-780.
Lane, M. C., P. W. O'Toole, and S. A. Moore. 2006. Molecular basis of the interaction between the flagellar export proteins FliI and FliH from Helicobacter pylori. J. Biol. Chem. 281:508-17.
Ryan, K. A., N. Karim, M. Worku, C. W. Penn, and P. W. O'Toole. 2005. Helicobacter pylori flagellar hook-filament transition is controlled by a FliK functional homolog encoded by the gene HP0906. J. Bacteriol. 187:5742-50.
Ryan, K. A., N. Karim, M. Worku, S. A. Moore, C. W. Penn, and P. W. O'Toole. 2005. HP0958 is an essential motility gene in Helicobacter pylori. FEMS Microbiol. Lett. 248:47-55.
Patterson, M. M., P. W. O'Toole, N. T. Forester, B. Noonan, T. J. Trust, S. Xu, N. S. Taylor, R. P. Marini, M. M. Ihrig, and J. G. Fox. 2003. Failure of surface ring mutant strains of Helicobacter mustelae to persistently infect the ferret stomach. Infect. Immun. 71:2350-5.
Other recent publications
Kagawa, T. F., W. O'Toole P, and J. C. Cooney. 2005. SpeB-Spi: a novel protease-inhibitor pair from Streptococcus pyogenes. Mol. Microbiol. 57:650-66.
Huang, J., P. W. O'Toole, W. Shen, H. Amrine-Madsen, X. Jiang, N. Lobo, L. M. Palmer, L. Voelker, F. Fan, M. N. Gwynn, and D. McDevitt. 2004. Novel chromosomally encoded multidrug efflux transporter MdeA in Staphylococcus aureus. Antimicrob. Agents Chemother. 48:909-17.
Research Programme: Genomics of pathogenic and probiotic bacteria
Overview Projects Positions Acknowledgments
My lab has two parallel programmes, on the human gastric pathogen Helicobacter pylori, and the human probiotic bacterium Lactobacillus salivarius.
H. pylori is a gastric pathogen colonizes more than 50% of the world's population - but the majority of infected people do not get severe disease. Unfortunately, in those that do have symptoms, they can range from mild gastritis, through to stomach and duodenal ulcers, and even gastric cancer, or lymphoma.
Lb. salivarius, in complete contrast, is a human probiotic strain. Probiotic bacteria are generally LAB which colonize the human GI tract, and confer a range of benefits upon the host - competition with pathogens, stimulation of certain immune parameters, reduction in inflammation or dietary intolerance, reduction of serum cholesterol.
We use Systems Biology - a combination of bioinformatics, functional genomics, proteomics and transcriptomics - to study how H. pylori and Lb. salivarius interact with the human gastrointestinal tract. To a degree, these two bacterial species - a pathogen and a probiotic - are opposite sides of the same coin. As shown in the diagram, they both have an intimate, long-term interaction with the host - with profoundly different outcomes. We are using Systems Biology to identify genes and gene products that are involved in the colonization and survival of these bacteria in the human GI tract. The long term goal is to interfere with H. pylori colonization (through vaccines or therapeutics), and to exploit probiotics for human health through functional foods. Both projects are housed in the Department of Microbiology and the Alimentary Pharmabiotic Centre (http://apc.ucc.ie).
Projects
H. pylori We are using molecular genetics, biochemistry, and structural biology (X-ray crystallography) to study how flagellar proteins interact to accomplish export and controlled assembly of the flagellum on the cell surface. H. pylori produces a range of other surface proteins involved in adhering to the gastric epithelium, and eliciting an inflammatory response. We are currently examining the production and export of adhesins of Helicobacter pylori, using a combination of microarrays, proteomics, high-throughput mutagenesis, and in vitro adhesion assay. In collaboration with the Pathogen Sequencing Unit of the Wellcome Trust Sanger Institute, we are undertaking a genomic analysis of Helicobacter mustelae (http://www.sanger.ac.uk/Projects/H_mustelae). H. mustelae infection of ferrets is the only natural model of Helicobacter-associated ulcer disease. Comparative and functional genomic studies will provide new insights into the molecular pathogenesis of human gastric disease.
Lb. salivarius In collaboration with colleagues at UCC and the Alimentary Pharmabiotic Research Centre, we are using functional genomics to identify genes and proteins which contribute to the probiotic effect exerted by these bacteria. To accomplish this, we have sequenced the genome of Lactobacillus salivarius subsp. salivarius UCC118. We have completed a bioinformatics analysis of putative adhesins and surface proteins, and we are testing their function by gene knock-outs and a variety of functional assays. We are designing custom microarrays for global transcript analysis. We are also developing genetic tools to facilitate functional assay of genes and proteins suspected of involvement in host interaction.
Positions
There are currently no positions
Acknowledgments
Work in Paul O'Toole's lab is supported by:
The Irish Research Council for Science, Engineering and Technology http://www.ircset.ie/
Science Foundation Ireland http://www.sfi.ie
