Modelling Gut Pathogen - Commensal Interactions GAMIDI (WP7)/ ER-3/C2/C3 Gerard Fleming CHEMOSTAT TECHNOLOGY LABORATORY Postgraduate Students: Paul Mc Cay (completing Ph.D.) David Mc Carthy (completing Ph.D.) Maurice Martyn (starting part-time M.Sc.) Olivia Duignan (Ph.D. with Dr. Carroll) Post-Doctoral Investigator: Dr. Alain A. Ocampo Sosa (joined Nov ’07) Deep-Ocean Post Doc – February 08 Strategic Areas of Research Microbial Evolution in Continuous Cultures Mutation, selection and competition in single-stage chemostats Microbial adaptation to selection pressures Deep Ocean Microbiology Keystone metabolically active microorganisms Laboratory culture of obligate piezophiles Aquaculture/ Bioaerosols Method validation: Antimicrobial Susceptibility Testing Novel biocides for the aquaculture sector Endotoxin levels in bioaerosols GAMIDI (WP7) The Pathogens: The Commensals: Campylobacter jejuni, Salmonella enterica, and Listeria monocytogenes Escherichia coli, Bacteroides spp., Lactic acid bacteria Why Continuous Culture ? Plug /continuous flow Extended period of culture Competition exclusion Mutation and selection Mutation / Selection in Practice: P. aeruginosa adaptation to biocide BKC MIC 250 150 -1 BKC (mg l ) 200 100 50 0 0 50 100 Generations elapsed BKC Conc supplemented in culture Population MIC (BKC) 146 The Work Package Population level Colonisation / exclusion rates in single and multistage chemostats +/Matrices Efficacy of clinical and sub-clinical levels of antibiotics on microbial persistence Influence of growth conditions on competitive indices Modelling of competition dynamics Molecular level Adherence / exclusion influences Nature of Intrinsic / acquired mutations resulting in enhanced competitiveness Gene regulation with particular reference to MDR efflux pumps Needs/ Collaborations Mathematical Modelling Capability Dr. Saji Varghese (Physics) and other collaborators Molecular Analysis Genetic analysis of mutants and capability to make “knock-out” mutants Microarray analysis up/down regulation of genes Molecular analysis at the protein level FISH