RESTORING SENSITIVIT (266717)

  https://cordis.europa.eu/project/id/266717

  FP7 (2007-2013)

  Rendering environmental pathogens sensitive to antibiotics prior to infection

  Marie Curie Action: "Reintegration Grants" (FP7-PEOPLE-2009-RG)

  virology  ·  immunology  ·  antibiotics  ·  antibiotic resistance  ·  molecular biology

  2010-09-01 Start Date (YY-MM-DD)

  2014-08-31 End Date (YY-MM-DD)

  € 100,000 Total Cost

  Description

Antibiotic resistance of pathogens is an accelerating problem and there is an urgent need for new antimicrobial agents. Pharmaceutical companies face numerous obstacles in developing new antibiotics, and therefore a method that will re-sensitize pathogens to well-established antibiotics harbors key advantages. We propose a system that restores antibiotic efficiency by reversing resistance of pathogens. The system utilizes bacteriophages, which possess engineering capabilities and are excellent, protected delivery vehicles. Unlike bacteriophage therapy, the proposed system does not rely on the ability of the phages to kill pathogens, but instead, to deliver genetic constructs to nosocomial pathogens rendering them sensitive to antibiotics prior to host infection. Pathogen-specific phages will be engineered with genes conferring sensitivity to an antibiotic of choice in a dominant fashion and small RNAs that target preferred resistance genes. Including a resistance marker to tellurite, a compound toxic to bacteria, will be used to generate a selective pressure, enriching for pathogens that harbor the phages. Genetic systems and molecular biology techniques will be used to maintain the phage in the pathogens and to ensure their transfer only as a complete unit, thus enhancing efficiency and providing safety measures. The proposed system may be used to render the pathogens susceptible to multiple antibiotics in a single construct. This will dramatically reduces evolvement of simultaneous resistance against multiple antibiotics. Extended treatment with the tellurite and the engineered phage will significantly enrich for antibiotic-treatable pathogens in nosocomial infections and in vast contrast to antibiotics and phage therapy, will change the nosocomial infections more susceptible to the proposed treatment. Moreover, the approach evades phage usage in the patient thus overcoming toxicity issues and neutralization of the phage by the spleen and the immune system.

  Complicit Organisations

2 Israeli organisations participate in RESTORING SENSITIVIT.