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ERA-NET PathoGenoMics Meeting Bonn 7-8 April, 2005

ERA-NET PathoGenoMics Meeting Bonn 7-8 April, 2005. Research topics of interest in the Area of Genomics of Bacterial and Fungal Pathogens of Humans. Prof. Francisco García-del Portillo External Advisory Board. Spain. March 16, 2005 Meeting at the Spanish Ministry Education and Science.

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ERA-NET PathoGenoMics Meeting Bonn 7-8 April, 2005

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  1. ERA-NET PathoGenoMics Meeting Bonn 7-8 April, 2005 Research topics of interest in the Area of Genomics of Bacterial and Fungal Pathogens of Humans Prof. Francisco García-del Portillo External Advisory Board. Spain.

  2. March 16, 2005 Meeting at the Spanish Ministry Education and Science • Attendees: • Dr. Rosa Rodriguez Bernabé (Head of Life Science Department) • Dr. José Antonio Salas (Life Science Department) • 10 Representatives of groups working in Bacterial Pathogenesis • Dr. F. García-del Portillo

  3. March 16, 2005 Meeting at the Spanish Ministry Education and Science • Topics discussed: • Interest and opportunity of research in human bacterial and fungal pathogens • Future areas of research in Genomics of pathogenic microbes • Interactions between public and private Entities • Search of common interests with other European conuntries

  4. Major Areas of Interest • How do highly pathogenic microbes emerge? • Microbial population, diversity and evolution of virulence • How do microbes cause disease? • Molecular mechanisms underlying pathogenicity (bacteria-host interaction) • Mechanisms of antibiotic resistance Which pathogen functions can be used as targets for diagnosis, prevention and treatment? • Comparative and functional genomics

  5. Genomics and Microbial populations (I) PFGE, MLEE, MST: limitation in resolving power for biodiversity studies How representative of a bacterial species are the available microarrays? Best of the cases: contain non-redundant set of genes of 3-4 strains Scarce genome information on “epidemic” clones: Streptococcus pneumoniae multiresistant epidemic “international” clones: Spain23F-1, Spain6B-2

  6. Genomics and Microbial populations (II) Genes specific to environmental clones Genes specific to epidemic clone 1 Epidemic strain 1 (2,3,4…) Annotation tasks “Core” genome Food Epidemic clones 5,6,7.. Environment Risk-indicator genes ? Humans Animals Genes specific to epidemic clone 2 DNA-DNA hybridization Advantage: LIMITED SET OF GENES OF EPIDEMIC STRAIN 1 TO STUDY AT A FUNCTIONAL LEVEL Proposal of indicator genes (exclusive of all epidemic clones) Expression, functional analysis

  7. Our experience and infrastructures… • “Genome Sequencing Units” • University of Valencia • Scientific Park of Madrid. http://www.pcm.uam.es/ • Scientific Park of Barcelona. http://www.pcb.ub.es/ • Annotation, microarray design • Listeria (EC-funded project) • Brucella mellitensis “re-annotation” • Endosymbionts (Buchnera, Blochmannia) • Oligonucleotide-based Salmonella microarray • Infection models for functional analysis of candidate genes • Extracellular and intracellular pathogens (in vitro & in vivo models): Salmonella, Listeria, Mycobacterium, Brucella, Staphylococci, Streptococci,..

  8. Microarray “strain” Microbe-host interactions • Interest in promoting further studies in “model” pathogens and “infection models” (host cell type, tissue tropism) • Microarrays covering the entire genome of the strain/clone used in the study 2 1 Test strain (virulent) In vitro In vivo ~ 8-10 % genome “non-represented” in the transcriptome (virulence genes?) Correspondence of phenotypes observed in both systems

  9. The “SALGENOMICS” Project Biofilm Cell division Intracellular persistence model Dam methylation DNA-binding proteins • Microarray representing 100% of the genome of the virulent reference strain used in all models

  10. PATOGENOM “A Network funded by the Spanish Ministry of Education and Science to create new and foster existing collaborations among groups that apply genome wide-based technologies to study human pathogens” http://www.cnb.uam.es/redpatog/

  11. PATOGENOM • 17 groups : • Candida albicans • Salmonella spp. • Escherichia coli (EHEC, EPEC) • Brucella mellitensis • Mycobacterium tuberculosis • Listeria monocytogenes • Streptococcus pneumoniae • Staphylococcus aureus • Topics/interests : • Bacteria-host cell interaction - Invasion, control of intracellular growth - Phagosome trafficking - Cell tropism • Gene regulation • Biofilm • Persistent infections • Antibiotic resistance Identification of new targets Diagnosis/treatment/vaccination http://www.cnb.uam.es/redpatog/

  12. Research Areas of Interest Comparative genomics (epidemic strains, multiresistant clones, model pathogens) * Some genes might not be expressed unless pathogen encounters the host !! Genome sequencing annotation PATOGENOM + Campylobacter spp. Helicobacter pylori * Infection models Transcriptome analysis (Host & pathogen) * Persistence, chronic infection Functional post-genomics Proposal of new targets DIAGNOSIS TREATMENT PREVENTION

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