Pathogenomics Goal: Identify previously unrecognized mechanisms by which bacteria cause disease, using a unique combination of informatics, evolutionary biology, microbiology and genetics.

Pathogenicity Processes that pathogenic bacteria use to cause disease are still minimally understood Bacterial proteins identified that manipulate host cells by interacting with, or mimicking, host proteins. Idea: Could we identify novel disease factors by identifying bacterial genes more similar to host genes than you would expect based on evolutionary relationships?

Informatics screen for candidate bacterial genes. - genes similar to host genes Rank candidates. - how much like host protein? Prioritize for further biological study. - previously studied? - UBC microbiologists study bacterium? - gene in model host that UBC geneticists may study? Evaluate evolutionary significance. Modify screening method Initial Approach Collect gene data

New gene data available for many pathogens AnthraxPlague Cat scratch diseasePeptic ulcers ChlamydiaPneumonia CholeraPeriodontal disease Dental cariesParatyphoid/enteric fever Diarrhea (E. coli etc.)Salmonellosis DiphtheriaScarlet fever Epidemic typhusShigellosis (bacillary dysentery) Mediterranean feverSleeping sickness Gastroenteritis Strep throat GiardiaSyphilis GonorrheaToxic shock syndrome Legionnaires' disease Tuberculosis LeishmaniasisTularemia LeprosyTyphoid fever LeptospirosisUrethritis Listeriosis Urinary Tract Infections Lyme diseaseWhooping cough MalariaMeningitis Necrotizing fasciitisYeast infection Some hospital-acquired infections, animal/plant infections

First finding: Surprising evidence of transfer of a gene from a bacterial pathogen to a protozoan pathogen ProtozoaBacteria Why did we find this? Why do we care?

Evidence that a gene was transferred between a bacterial pathogen and a protozoan pathogen H. influenzae: Causes respiratory tract infections and meningitis T. vaginalis: Causes the STD Trichomonas A gene in the bacterium Haemophilus influenzae, and related bacteria, is highly similar to a gene in the protozoan Trichomonas vaginalis.

Evidence that a gene was transferred between a bacterial pathogen and a protozoan pathogen Unusual occurrence of gene transfer. Did this gene transfer confer a benefit to Trichomonas? In bacteria: - Gene participates in system that parasitizes the mucous membranes of animals for nutritional purposes. - Definitive role in disease still unstudied In this protozoan: - Similar role?

Publication in Preparation Keeling, Patrick F., Fiona S. L. Brinkman, Audrey de Koning and Steven J. Jones. “Evidence supporting horizontal gene transfer from a pathogenic bacteria to a pathogenic protozoan.” To be submitted to the journal Molecular Biology and Evolution.

Back to the focus: Identifying bacterial genes similar to host genes

Pathogenomics Database

World Research Community Prioritized candidates Study function of similar gene in model host, C. elegans. Study function of gene. Investigate role of bacterial gene in disease: Infection study in model host Further biological study The worm C. elegans DATABASE Contact other groups for possible collaborations.

Summary: Strengths Interdisciplinary team Automated informatics approach - continually updated Better understanding: pathogen gene and similar host gene Insight into gene transfer events between organisms and evolution of pathogen-host interactions Public database: –Exposure for UBC research –Foster collaborations –Benefit world research community

Pathogenomics group –Ann M. Rose, Yossef Av-Gay, David L. Baillie, Fiona S. L. Brinkman, Robert Brunham, Stefanie Butland, Rachel C. Fernandez, B. Brett Finlay, Robert E.W. Hancock, Christy Haywood-Farmer, Steven J. Jones, Patrick Keeling, Audrey de Koning, Don G. Moerman, Sarah P. Otto, B. Francis Ouellette, Iain E. P. Taylor. Peter Wall Institute for Advanced Studies Acknowledgements