“Applied pathogenomics: Prevention, diagnosis, treatment and monitoring of infectious diseases in
humans”
| Project No. |
Coordinator |
Project Partners |
(Short) Title
|
| 10 |
Ulrich Vogel |
Seppo Meri
Muhamed-Kheir Taha
Jan Poolman |
Genome wide screening of the human pathogen
Neisseria meningitidis for proteins enhancing serum resistance and
evaluation of their vaccine potential |
| Neisseria meningitidis (meningococcus) continues to be a major health threat by causing
septicaemia and meningitis with a case fatality rate of ~10%. A major line of immune defence against meningococci is the serum
complement system, but certain serogroups are able to evade the immune response, leading to a limited strain coverage of current
vaccines. 4 research groups from 3 countries undertook to develop novel vaccines that will generate antibodies capable of blocking
bacterial factors involved in immune escape. To this end, a systematic genomic approach is proposed, in order to uncover
complement regulatory molecules in meningococci. |
| 12 |
José Antonio Bengoechea |
Philippe Sansonetti
Thomas F. Meyer
Thomas Rudel
Carmen Buchrieser
Joerg Poetzsch |
Functional genomics of host-pathogen interactions
using high-throughput screenings: a novel approach towards identifying
therapeutic/prophylactic targets |
The progress of infections is the joint outcome of both pathogen and host-related
features. This project, comprising 6 research groups from 3 countries, aims to identify novel pathogen determinants targeting
crucial host functions, using genomic, bioinformatics and high-throughput screening methods.
The group will focus on 5 important human pathogens: M. tuberculosis, L. pneumophila, H. pylori, N. gonorrhoeae and K. pneumoniae.
The project complements ongoing work in the RNAi-Net, which focuses on the host side. This research program is expected to lead
to the development of innovative therapies based on the modulation of the hostpathogen interface.
|
| 16 |
Ulrich Dobrindt |
Jörg Hacker
Timo Korhonen
Levente Emődy
Istvan Wittmann
Eliora Ron
Catharina Svanborg; Björn Wullt |
Pathogenomic approach to explore the use of
bacterial interference as alternative treatment of recurrent urinary
tract infections |
| There is a strong need for alternatives to current antibiotic treatment, such as
"bacterial interference", vaccination and new drugs. This project brings together 6 research groups from 4 countries to
understand the molecular basis of asymptomatic bacteriuria (ABU) and to apply genomic approaches to exploit ABU E.coli isolates
for "bacterial interference" to combat recurrent UTI. The acquired data will also provide additional information on bacterial
traits that are associated with symptomatic infection, thus helping to identify new vaccine or drug targets for combating UTI.
The geno- and phenotypic stability of isolate 83972 will be studied allowing its further improvement for bacterial interference.
|
| 21 |
Sophie de Bentzmann |
Patrick Plésiat
Juan Luis Ramos
Isabel Sá-Correia
Soeren Molin
Catherine Nguyen
Matilde Fernández |
ADHRES-Signature Project |
| Targeting bacterial virulence rather than survival may offer a reduced selection pressure for
drug-resistant mutations. The most common virulence trait is abacterial community called biofilm, which is highly resistant to
antibiotic treatment and host defences. P. aeruginosa, P. putida and B. cepacia complex are particularly problematic, since they
constantly exist as biofilm. The goal of this consortium, of 7 research groups from 4 countries, is to identify a core set of
genes involved in biofilm and antimicrobial resistance important in in vivo infectious situation and relevant to clinical
pathogenicity. Such a gene list is patentable, and amenable to screening by chips or any other technique for mRNA detection.
|
| 29 |
Torsten Hain |
Maja Rupnik
Axel Hartke
Bernd Kreikemeyer
Susanne Engelmann
Sonja Vorwerk
Thomas Hartsch |
sncRNAomics - High throughput comparative
sncRNAome analysis in major Gram-positive human pathogenic bacteria:
functional characterization by a systems biology approach and peptide
nucleic acid drug design |
| Novel anti-infectives are of high priority for global health care. Small non-coding RNAs
(sncRNAs) in bacteria are an emerging class of new gene expression regulators, but their role in colonisation and pathogenicity
is largely unknown. The consortium brings together 7 research groups from 3 countries, thus combining novel high-throughput
sncRNA screening methods, whole-genome transcriptomics and proteomics and bioinformatics coupled with molecular characterization
methods to provide new data regarding sncRNAs in major high-risk Grampositive microbes (e.g. Staphylococcus, Streptococcus,
Enterococcus, Clostridium and Listeria). Potential new drugs and diagnostic biomarkers will be validated using tissue-culture
and subsequently in in-vivo models.
|
| 35 |
Antonio Di Pietro |
Hubertus Haas
Gerhard Braus
Sven Krappmann
Ana Conesa
Roland Beffa |
Transcriptional networks controlling virulence in
filamentous fungal pathogens (TRANSPAT) |
| Invasive fungal infections in immunocompromised patients are on the rise, in particular of
filamentous species (moulds). Still, little is understood about the ability of filamentous fungi to survive in the hostile
environment of mammalian blood. Even less is understood about their clinical resistance to antifungal agents. TRANSPAT,
comprising 6 research groups from 4 countries, aims to integrate genetic, genomic and bioinformatic tools to uncover clinically
relevant transcriptional networks in fungi, exploiting the complete genome sequences and mutant collections of A. fumigatus
and F. oxysporum. This approach will identify gene sets showing altered expression during invasive infection and/or exposure
to antifungals.
|
| 36 |
Axel Brakhage |
Jean-Paul Latgé
Emilia Mellado Terrado
Fernando Pelaez
Dominique Costantini
|
The cell wall as a target to improve antifungal
therapy against Aspergillosis |
| Aspergillus fumigatus infections have dramatically increased worldwide. Due to the limited
number and efficacy of antifungal drugs, the mortality from Invasive Aspergillosis (IA) is very high. The cell wall of
A. fumigatus is a major drug target. This project aims at elucidating the relationship between signal transduction cascades
and cell wall biosynthesis in A. fumigatus, leading also to the identification of drug-resistance mechanisms. Functional genomic
analyses, large-scale mutant libraries and genetic reporter systems will be the key methodologies, employed by 5 research groups
from 3 countries. The tools generated may lead to new, more efficient drugs.
|
| 37 |
Maja Rupnik |
Bruno Dupuy
Frederic Barbut
Adriano O. Henriques
Alexander Indra
Wolfgang Liebl |
Pathogenomic of increased Clostridium difficile
virulence |
| Clostridium difficile is increasingly associated with infections in hospitals and in the
community, and hypervirulent types are emerging. Six research groups from 5 countries undertook this project, aiming to use
genomic approaches to study C. difficile types with increased virulence and to analyze the presence of known and new virulence
factors, regulation of their expression and genomic heterogeneity. The expected results will be valuable for recognizing,
monitoring and diagnosing virulent types, improved prevention, and better treatment.
|
| 41 |
Matthias Maass |
Kamil Önder
Mirja Puolakkainen
Dezso Peter Virok
Johann Bauer
Martha Böttcher |
Transcriptome-based Monitoring and Eradication of
Chronic Chlamydial Infection - ChlamyTrans - |
| ChlamyTrans is a consortium of two commercial and four academic partners to study the
pathogenomics of chronic Chlamydia infection. Genital Chlamydia trachomatis infection is the leading sexually transmitted
disease and Chlamydia pneumoniae is a frequent cause of respiratory infection and linked to atherosclerosis in genetically
susceptible individuals. The key for the chlamydial pathobiology is the ability of the pathogen to enter a non-replicative
antibiotic-resistant state due to reprogramming of the host cell metabolism. The objective of ChlamyTrans is to use two
complementary genome-wide transcriptomics approaches to produce commercially exploitable products for monitoring, treating
and ultimately preventing chronic chlamydial infections.
|
| 44 |
Pavel Kovarik |
Emmanuelle Charpentier
Ilkka Julkunen
Sylvia Knapp
Claire Poyart
Estzter Nagy |
Mechanisms and modulation of innate immune
responses to Streptococcus pneumoniae and S. pyogenes |
| Pharmacological modulation of pathogen recognition is a promising, approach to adjust the
strength of immune responses. In this project, the recognition of Streptococcus pneumonia and Streptococcus pyogenes by the
host innate immune cells will be studied on a whole-genome scale. These bacteria are still a major health concern and are also
acquiring widespread resistance to antibiotics. The clinical manifestations of these pathogens are highly variable, partly due
to differential recognition of the pathogens by the innate immune system. The project, jointly carried out by 5 academical
research groups and one biotech company from 3 countries, will identify novel players in streptococcal diseases and develop
strategies leading to modulation of the host's immune response.
|
| 45 |
Thomas Rattei |
Johannes Hegemann
Romé Voulhoux
Agathe Subtil
Matthias Horn
Jan Rupp
Ana Conesa Cegarra |
Host-pathogen protein-protein interactomes and
their influence on the host metabolome |
| Bacterial protein secretion is a key mechanism underlying infection, pathogenesis and
modulation of the host cells. In this project, novel biomarkers and drug target candidates will be developed for the diagnosis
and therapy of Pseudomonas aeruginosa and Chlamydiae infection. Both pathogens secrete effector proteins into their host cells,
and share a high prevalence of infection and disease, limited diagnostics and unspecific therapy. This project benefits from the
combined efforts of 7 research groups from 4 countries, and will contribute considerably to the therapeutic efforts targeting
these pathogens by developing novel diagnostic strategies and biomarkers and identifying drug target candidates.
|
| 49 |
Stephan Ott
Co-Coordinator: Vítor Martins dos Santos |
Manuel Ferrer
Andres Moya
Laya Pedrola
Bernhard Ronacher
Miguel Godinho |
Development, prevention and early diagnostic
detection of Clostridium difficile-associated pseudomembranous colitis -
an interdisciplinary network |
| Pseudomembranous colitis is an infectious disease of the human colon, mostly caused by
Clostridium difficile. A major aetiology of pseudomembranous colitis is the use of broadspectrum antibiotics, which lead to
an altered intestinal microflora and to activation or overgrowth of C. difficile. The goal of the project network, comprising
7 research groups from 4 countries, is to characterize the composition and metabolic/functional status of intestinal microflora
from the non-diseased stage towards C. difficile-associated pseudomembranous colitis in the human system, thereby enhancing our
understanding of this disease and paving the road for the early diagnosis and effective prevention and intervention strategies.
|
| 50 |
Alexander Mellmann |
Dorothea Orth
Nicolas Barnich
Eduard Torrents |
Identification of hot spots of divergence and
rapidly changing genes within Shiga toxin-producing Escherichia coli
|
| Identification of hot spots of divergence and rapidly changing genes within Shiga
toxinproducing Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli
strains have acquired specific virulence factors, allowing them to cause a broad spectrum of human diseases. This project,
which represents a multi-disciplinary collaboration of four research groups from Austria, France , Germany and Spain, will
focus on Shiga toxin-producing E. coli (STEC) and on Adherent-Invasive E. coli (AIEC), two intestinal pathogenic subgroups of
E. coli. The results of this project will lead to a new understanding of basic principles of pathogenesis, to improvement of
diagnosis and typing, and to establishing of new preventive and therapeutic approaches.
|
