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.