Disrupting drug resistance by exploiting collateral sensitivity to design novel therapeutic strategies for C. auris and C. glabrata (CycleDrug)




Multidrug resistance is a major problem in Candida auris, the first pathogenic fungus officially considered an urgent antimicrobial resistance threat by the CDC, and in Candida glabrata, which accounts for 20-40% of all systemic Candida infections. Antifungal resistance often leads to treatment failure, which significantly reduces survival rates of lethal candidiasis. Meanwhile, the antifungal drug market comprises only four classes.

By evolving C. auris and C. glabrata in different drugs and mapping their responses to other drugs, we have discovered collateral sensitivity (CS) and cross resistance (XR). CS is the process in which the acquisition of drug resistance towards one drug, confers an increased sensitivity towards another drug. Conversely, XR confers reduced susceptibility to more than one drug upon exposure to one drug. Information regarding the evolutionary tendencies of pathogenic fungi can be leveraged to improve therapeutic approaches for treating fungal infections. Both CS and XR have been studied extensively in tumors and in bacteria but remain unexplored in fungi. In this study, we will explore novel treatment schemes that have the potential to prevent the development of antifungal drug resistance in MDR species of most concern: C. auris and C. glabrata.

Project partners

  • Patrick Van Dijck, Katholieke Universiteit Leuven, Belgium (Coordinator)
  • Katrien Lagrou, University Hospitals Leuven, Belgium
  • Johan Maertens, University Hospitals Leuven, Belgium
  • Micha Fridman, Tel Aviv University, Israel
  • Juan Antonio Gabaldon Estevan, Institute for Research in Biomedicine, Spain
  • Berman Judith, Tel Aviv University, Israel