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 !!