Strengthening current antibiotics to treat life-threatening resistant hospital-acquired infections

Xavier Daura

  • PROJECT LEADER

    Xavier Daura

  • HOST ORGANIZATION,
    COUNTRY

    UAB, Universitat Autònoma de Barcelona, Spain

  • DESCRIPTION

    Research
    Antimicrobial resistance (AMR) is considered by WHO a major global risk for human health. The situation is particularly critical regarding multidrug-resistant (MDR) Gram-negative (GN) bacteria, a main cause of hospital-acquired infections. There is therefore an urgent need to discover new molecular targets or modes of action for the development of antimicrobials less susceptible to resistance, together with strategies to enhance and rescue the effects of current drugs.

    Aim
    To develop antibiotic adjuvants and resistance breakers to enhance the effects of current antibiotics and reduce the AMR problem, by exploiting new protein targets in GN bacteria.

    Problem to Solve
    The emergence and spread of MDR bacteria limits the treatments available to fight the infections they cause, putting patients at risk. The effective control of bacterial infections concerns most medical specialties and is essential in surgery.
    The shortage of effective antibiotics to treat MDR GN bacteria in particular has forced clinicians to reintroduce the use of colistin in clinical practice as an emergency solution. Introduced over 50 years ago, colistin use was later discontinued due to its toxicity. However, some GN bacteria are developing resistance even against last-resort antibiotics such as colistin.

    Innovation
    AMB Advanced Therapeutics is a platform that targets proteins involved in the homeostasis of the cell envelope of GN bacteria. The team has already found that modified bacteria lacking one such protein have more permeable membranes, making them more susceptible to certain antibiotics such as colistin.

    Level of Innovation
    To date, the AMB Advanced Therapeutics platform has identified five small molecules that inhibit this target protein, making colistin more effective and reducing the resistance of tested strains. These adjuvant candidates could be used to lower the colistin dose, reducing the toxicity of the treatment, or increasing its effects.