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Infection biology training network: shaping the future of infectious diseases treatments

Final Report Summary - INBIONET (Infection biology training network: shaping the future of infectious diseases treatments)

The increasing number of bacteria resistant to all antibiotics and antimicrobials and the virtual lack of antiviral drugs make it necessary to develop therapeutics based on new targets/approaches. European-wide-acting sectors must permanently improve their capabilities and capacities to cope with these challenges. Thus, the demand for experts trained to understand infectious diseases in their whole complexity is rising. INBIONET is an initiative from seven academic groups internationally recognized in the fields of microbial pathogenesis, innate immunity and molecular recognition, an intensive research SME, Preclin Biosystems, a multinational pharmaceutical company, Sanofi-Aventis, and a technological park (ParcBit). INBIONET partners embarked on the analysis of bacteria, viruses and enteric parasites specified by various infection strategies to identify cellular pathways important for infection as well as pathogen determinants involved in disease progression.
INBIONET fellows have uncovered the crucial importance of type I IFNs in host defence against viral infections but also against bacterial human pathogens. INBIONET research programme has revealed new virulence strategies of vaccinia virus, helminths and the bacterial pathogens Klebsiella pneumoniae and Helicobacter pylori to manipulate innate immune signalling cascades for their own benefit. These research efforts also led to the identification of new virulence factors suitable to be targeted in drug discovery programmes. In turn, INBIONET fellows have generated compelling pre-clinical evidence for new therapeutics based on modulation of innate immune responses and enhancing the production of antimicrobial molecules. Finally, during INBIONET programme fellows have developed several cutting-edge models to investigate infectious diseases, chiefly organoids for gastric infections, in vivo model of virus-bacteria co-infection, and high-throughput assays to study pathogen’s effect on host posttranslational modifications.
Overall, INBIONET research programme, by bridging cellular and molecular microbiology and immunology, has provided mechanistic insights into the strategies used by a plethora of human pathogens to survive during infections (pneumonia and gastric infections). Furthermore, and by building up upon this knowledge platform, we have provided initial evidence demonstrating that therapeutic antagonism of these strategies may favour pathogen clearance. Harnessing the host-pathogen interface opens the avenue for new antimicrobial therapeutics. Interference with pathogen virulence and/or signalling pathways hijacked by pathogens for their own benefit is an especially compelling approach, as it is thought to apply less selective pressure for the development of resistance than traditional strategies, which are aimed at killing pathogens or preventing their growth. There are already drugs approved for use in humans which target some of these virulence strategies. From the drug discovery point of view, this significantly circumvents the drug development process hence allowing a potential fast-track transition from the basic research to clinical development. Altogether, we envision that our results will encourage other academics as well as pharmaceutical companies to follow this avenue of research to tackle the problem of lack of therapies for microbes resistant to antimicrobials.
The four-year INBIONET training programme, at the interface between microbiology, immunology and cellular biology, has trained a cohort of early career researchers in the competitive field of “microbial anti-immunology” and set the grounds for new preventatives and therapeutics. INBIONET academic and industrial partners did provide the necessary critical mass to offer a top level training not currently offered in such dimension by any European academic institution thereby giving trainees a thorough and truly interdisciplinary background to meet the demands of the European (scientific) labour market.

Project webpage: http://www.inbionet.eu
Project coordinator: Professor Jose Bengoechea (j.bengoechea@qub.ac.uk) , Queen’s University Belfast (UK).