Phage Therapy Antipersister strategy
( PHAGES-AntiPERS )

Therapeutics

Research Project: 2025-04-01 - 2028-03-31
Total sum awarded: €1 216 680

Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, the ESKAPE group members, are deemed critical pathogens by the WHO (Priority 1)due to their extensive resistance to antibiotics. While lytic phages are offered as alternative antibacterials, certain chronic infections retain bacterial persisters resistant to treatment.The PHAGES-AntiPERS consortium is a multidisciplinary team of clinicians, microbiologists, and bioinformaticians, focusing on the use the innovative therapeutic approaches that let to overcome the development of persister cells in chronic and biofilm-associated infections treated by lytic phages and antibiotics.We aim to design and verify “anti-persisters proof of concept strategies“ by antimicrobial combinations of antibiotics, lytic phages, phage-borne enzymes (endolysins and depolymerases), and anti-persister agents (toxin-antitoxin systems(TA),quorum sensing network (QS) and ppGpp signalling inhibitors). The eradication of persister bacteria will be investigated in vitro and in vivo for different antimicrobial combinations, accompanied by the analyses of the phenotypic and genomic basis of anti-persister activity both at the phage and bacteria levels.The PHAGES-AntiPERS initiative entails developing a reference database and biobank of K. pneumoniae, P. aeruginosa, and A. baumannii strains known to develop persistent infections. We are also establishing an AntiPERS Phage bank specifically tailored to target persister cells, providing a foundation for novel and effective treatments against antibiotic-resistant infections.

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  • Maria Tomás, Instituto de Investigación Biomédica A Coruña (Fundación Profesor Novoa Santos), Spain (Coordinator)
  • Jesus Oteo-Iglesias, National Center of Microbiology, Instituto de Salud Carlos III, Spain (Partner)
  • Zuzanna Drulis-Kawa, University of Wroclaw, Poland (Partner)
  • Ran Nir-Paz, Hadassah Medical center/Hebrew University, Israel (Partner)
  • Evelien Adriaenssens, Quadram Institute Bioscience, United Kingdom (Partner)
  • Jean-Paul Pirnay, Ecole Royale Militaire-Koninklijke Militaire School, Belgium (Observer)

Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, (the ESKAPE group), are recognized as critical pathogens, exhibiting resistance to multiple antibiotics and emerging therapies. Despite the promise, certain chronic infections still harbor resilient bacterial persisters even after phage therapy. To address this challenge, the PHAGES-AntiPERS consortium, comprising experts from diverse fields such as medicine, microbiology, and bioinformatics, is dedicated to pioneering innovative strategies. The consortium aims to combat the development of persister cells in chronic and biofilm-associated infections treated with lytic phages and antibiotics. Our goal is to devise and verify "anti-persisters proof of concept strategies" by combining antimicrobial agents like antibiotics, lytic phages, phage-derived enzymes (endolysins and depolymerases), and anti-persister compounds (toxin-antitoxin systems, quorum sensing inhibitors, and ppGpp signaling inhibitors). We will investigate the eradication of persister bacterial cells both in laboratory settings and in living organisms, assessing the phenotypic and genomic factors underlying anti-persister activity at both phage and bacterial levels. The success of PHAGES-AntiPERS relies on establishing a reference database and biobank of strains from K. pneumoniae, Pseudomonas aeruginosa, and A. baumannii prone to persistent infections. We are building also an AntiPERS Phage bank tailored to target persister cells thus laying the groundwork for innovative and effective treatments against persistent infections.

Call

2024 - Interventions moving forward to promote action to counteract the emergence and spread of bacterial and fungal resistance and to improve treatments