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Typ projektu

Scientific project


June 2023


Wroclaw, Munich, Berlin, Leuven, Paris, Jerusalem

Klebsiella pneumoniae is a critical pathogen (WHO priority 1) that displays pan-resistance against prevalent antibiotics. Moreover, capsular polysaccharides (K-antigen) are the key virulence factor protecting this bacterium against the human immune system response & harsh environments. The KLEOPATRA consortium is a multidisciplinary team of clinicians, microbiologists, bioinformaticians, focusing on the use of (bacterio)phages and their components (capsule depolymerases, CD) as sustainable combinations with antibiotics (AB). As natural predators of bacteria, some phages specifically recognize and target the K-antigen as a receptor for infection. In this proposal, we introduce the concept of K-sensitization, which utilizes capsule-specific (CS) phages and their CDs to drive bacteria towards capsule depletion. These (1) resensitize bacteria to the AB treatment, (2) sensitize Klebsiella to the host defence system, and (3) make strains susceptible to capsule-independent (CI) phages recognizing receptors hidden beneath the capsule layer. The envisioned K-sensitization preclinical proof-of-concept aims to develop a synergistic phage therapy/antibiotic treatment protocol against encapsulated pathogens that helps preserve the commensal microbiome diversity. The approach is supported by pheno- and genotype analyses of prevalent clinical & environmental isolates. Furthermore, the design of AB/phage/CD cocktails will be driven by tailored diagnostics tools, a unique phage production approach of dedicated phage banks and data-powered mathematical models for optimal synergy.

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