The multidrug-resistant bacteria Klebsiella pneumoniae represents a critically emerging pathogen that confounds treatment in a clinical setting. This is due to their pan-resistance to antibiotics and specific biological traits, including a protective capsule, that makes it insensitive to the host immune system.
Bacterial viruses, also called (bacterio)phages are natural predators of bacteria. Our previous research has identified phages that overcome the capsule barrier by specific enzymes and resensitize bacteria to the innate immune system as well as to antibiotic treatment.
In this project, we introduce the concept of “K-sensitization” which uses these phages and their enzymes (capsule depolymerases) to strip the protective capsules from prevalent K. pneumoniae strains and provide a proof-of-concept of how phages/depolymerases act synergistically to antibiotic treatment. Besides the development of a protocol for compassionate phage therapy against these encapsulated pathogens, we will comprehensively analyze the prevalent K. pneumoniae circulating in human & animal reservoirs, as well as environmental ecosystems. This in turn will lead to the establishment of tailored phage banks & associated diagnostics tools, supported by computational models to ensure rationally designed phage therapy cocktails for antibiotic/phage/enzyme combination treatments.
In this manner, the KLEOPATRA consortium aims to contribute to improving the treatment of this critical WHO priority 1 pathogen within a ‘One Health’ setting.
- Zuzanna Drulis-Kawa, University of Wroclaw, Poland (Coordinator)
- Rob Lavigne, KU Leuven, Belgium
- Regis Tournebize, Sorbonne Université, France
- Joachim J. Bugert, Bundeswehr Institute of Microbiology, Germany
- Jens Andre Hammerl, German Federal Institute For Risk Assessment, Germany
- Ronen Hazan, Hebrew University of Jerusalem, Israel
- Kilian Vogele, INVITRIS SME, Germany