ERA-NET PathoGenoMics Meeting Bonn 7-8 April, 2005
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Transcript of ERA-NET PathoGenoMics Meeting Bonn 7-8 April, 2005
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ERA-NET PathoGenoMics MeetingBonn 7-8 April, 2005
Research topics of interest in the Area of Genomics of Bacterial and Fungal
Pathogens of Humans
Prof. Francisco García-del PortilloExternal Advisory Board. Spain.
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March 16, 2005Meeting 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
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March 16, 2005Meeting 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
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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
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Genomics and Microbial populations (I)
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
PFGE, MLEE, MST: limitation in resolving power for biodiversity studies
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Genomics and Microbial populations (II)
“Core” genome
Genes specific to environmental clones
Genes specific to epidemic clone 1
Genes specific to epidemic clone 2
Risk-indicator genes ?
Epidemic strain 1 (2,3,4…)Annotation tasks
Food
Environment
Epidemic clones 5,6,7..
HumansAnimals
Proposal of indicator genes (exclusive of all epidemic clones)
Expression, functional analysis
DNA-DNA hybridization
Advantage: LIMITED SET OF GENES OF EPIDEMIC STRAIN 1 TO STUDY
AT A FUNCTIONAL LEVEL
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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,..
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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
Test strain(virulent)
~ 8-10 % genome “non-represented” in the
transcriptome(virulence genes?)
In vivoIn vitro
Correspondence of phenotypes observed in both systems
Microarray “strain”
1
2
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The “SALGENOMICS” Project
Cell divisionBiofilm
Dam methylationDNA-binding proteins
Intracellular persistence model
Microarray representing 100% of the genome of the virulent reference strain used in all models
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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/
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PATOGENOM
17 groups :
• Candida albicans
• Salmonella spp.• Escherichia coli (EHEC, EPEC)• Brucella mellitensis• Mycobacterium tuberculosis• Listeria monocytogenes• Streptococcus pneumoniae• Staphylococcus aureus
http://www.cnb.uam.es/redpatog/
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
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Research Areas of Interest
Transcriptome analysis(Host & pathogen)
Comparative genomics(epidemic strains,
multiresistant clones, model pathogens)
Proposal of new targets
Functional post-genomics
DIAGNOSISPREVENTION
TREATMENT
Infection models
Persistence, chronic
infection
Genome sequencing annotation
PATOGENOM +Campylobacter spp.Helicobacter pylori
* *
* Some genes might not be expressed unless pathogen
encounters the host !!