ANTIPATHOGN
Identification and validation of novel drug targets in Gram-negative bacteria by global search: a trans-system approach
| Coordinatore | UNIVERSITAT AUTONOMA DE BARCELONA
Organization address
address: Campus UAB -BELLATERRA- s/n contact info |
| Nazionalità Coordinatore | Spain [ES] |
| Totale costo | 7˙692˙588 € |
| EC contributo | 5˙943˙961 € |
| Programma | FP7-HEALTH
Specific Programme "Cooperation": Health |
| Code Call | FP7-HEALTH-2007-B |
| Funding Scheme | CP-FP |
| Anno di inizio | 2009 |
| Periodo (anno-mese-giorno) | 2009-02-01 - 2013-07-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
UNIVERSITAT AUTONOMA DE BARCELONA
Organization address
address: Campus UAB -BELLATERRA- s/n contact info |
ES (CERDANYOLA DEL VALLES) | coordinator | 966˙819.00 |
| 2 |
PROTEROS BIOSTRUCTURES GmbH
Organization address
address: AM KLOPFERSPITZ 19 contact info |
DE (MARTINSRIED) | participant | 848˙840.00 |
| 3 |
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Organization address
address: CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA contact info |
ES (BARCELONA) | participant | 744˙320.00 |
| 4 |
DEUTSCHES KREBSFORSCHUNGSZENTRUM
Organization address
address: Im Neuenheimer Feld 280 contact info |
DE (HEIDELBERG) | participant | 698˙879.00 |
| 5 |
BIO-XTAL SARL
Organization address
address: ROUTE DE LA CHAPELLE 227 contact info |
FR (ST FELIX) | participant | 541˙040.00 |
| 6 |
"MICROBIONTA, S.L."
Organization address
address: Ronda de Poniente - Bajo C-D 4 contact info |
ES (Tres Cantos) | participant | 533˙273.00 |
| 7 |
InterMed Discovery GmbH
Organization address
address: Otto-Hahn-Strasse 15 contact info |
DE (Dortmund) | participant | 471˙063.60 |
| 8 |
RPS RESEARCH IBERICA SL
Organization address
address: VIA AUGUSTA 21-23 contact info |
ES (BARCELONA) | participant | 419˙865.72 |
| 9 |
FUNDACIO PRIVADA CLINIC PER A LA RECERCA BIOMEDICA
Organization address
address: CARRER ROSSELLO 149-153 contact info |
ES (BARCELONA) | participant | 356˙720.00 |
| 10 |
ANAXOMICS BIOTECH, S.L.
Organization address
address: CALLE BALMES (PISO 4 - PTA 2A) 89 contact info |
ES (Barcelona) | participant | 231˙544.28 |
| 11 |
HELMHOLTZ-ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH
Organization address
address: Inhoffenstrasse 7 contact info |
DE (BRAUNSCHWEIG) | participant | 131˙596.40 |
Mappa
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Obiettivo del progetto (Objective)
'Multi-drug-resistant bacterial infections are increasing at an alarming pace in both developing and developed countries and in both community and nosocomial settings. The few antimicrobial agents that have been launched during the last decade (e.g. linezolid, daptomycin) have a good activity against Gram-positive bacteria. However, multi-drug-resistant bacteria are often found among the Gram-negative group. To tackle this problem, the AntiPathoGN project proposes a novel strategy for the discovery of new antimicrobial drug targets in a number of Gram-negative bacteria. This strategy is based on a comparative, system-level analysis of molecular processes involved in pathogenicity, drug resistance, cell division and/or growth of selected pathogenic Gram-negative bacteria through a combination of computational biology, interactome discovery, in-vivo protein-blocking and structural biology techniques. This comparative analysis, at one organization level above genomics, shall permit the discovery of new potential drug targets, relevant to both species-specific and broad-spectrum antimicrobial strategies. In addition, the AntiPathoGN project will pursue the identification of novel antibacterial compounds acting against previously validated targets by screening purpose-specific libraries of products derived from natural resources and from synthetic compounds. An important aspect of the project is that more than one approach is planned for the key objectives of target identification, target validation, target characterisation, and hit finding. The AntiPathoGN consortium is composed of 1 university bringing expertises in computational biology and microbiology, 3 research centres with expertises in computational and experimental interactomics, structural biology and clinical microbiology, and 7 SMEs with records on recombinant-antibody technology, structural biology, drug discovery and clinical research. The AntiPathoGN project fully addresses topic HEALTH-2007-2.3.1-1.'
Introduzione (Teaser)
Multidrug-resistant (MDR) bacteria constitute one of the major threats to public health worldwide. The lack of new antimicrobial drugs available on the market is fuelling the spread of MDR infections.
Descrizione progetto (Article)
The shortage of antibiotics for MDR infections caused by gram-negative bacteria is particularly critical. Bacteria from this group are the main cause of death among patients with hospital-acquired infections. The cell structure of gram-negative bacteria makes them more difficult to attack with drugs than gram-positive organisms.
Existing antibiotics target mechanisms or structures that are essential for bacterial survival or growth. This offers a rapid solution, but leads to possibility of MDR bacteria selection. Alternative strategies target mechanisms related to development of infection.
The EUfinanced the http://www.antipathogn.eu (ANTIPATHOGN) project to discover new targets and treatments that are less prone to development of drug resistance. ANTIPATHOGN studied mechanisms related to pathogenicity of Gram-negative bacteria to find new drug targets, or combinations of targets, and active compounds against them. The researchers focused on high-priority MDR bacteria such as Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Helicobacter pylori and Stenotrophomonas maltophilia.
A major achievement of ANTIPATHOGN was the generation of a database of protein interaction (interactome) networks available for gram-negative bacteria. The consortium has identified phenotypically and validated 18 potential antimicrobial targets in gram-negative bacteriaand found potential drugs against two of them. Two of the targets are essential for bacterial growth, while the other sixteen are involved in various mechanisms related to virulence or resistance.
Cell-based screens have identified 33 natural products with antimicrobial activity, including 3 novel compounds. Further studies will confirm the potential of these targets and compounds for antimicrobial drug development.
The results of the project have been presented at 19 scientific conferences and have produced 54 publications in top-ranking journals. Information about new developments of ANTIPATHOGN is available through its website.
The databases and tools generated by ANTIPATHOGN constitute a fundamental contribution to the knowledge platform on MDR bacteria. The consortium has provided new data on the biology of gram-negative bacteria and transformed them into tools that can be used for the development of new drugs for MDR bacteria.