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.
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
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
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
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
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
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,..
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
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
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/
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
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 !!