SaPhaDe · Know your enemy: systematic discovery of Salmonella anti-Phage Defences for the improved design of phage therapeutics

Know your enemy: systematic discovery of Salmonella anti-Phage Defences for the improved design of phage therapeutics

Summary SaPhaDe project Antimicrobial drug resistance is a serious global threat that make us to fear the return of the mortality rates from pre-penicillin times. A promising alternative to antibiotic drugs is the phage therapy, which is based in viruses that kill bacteria. The rational design of effective phage therapeutics requires a fundamental understanding of evolutionary co-adaptation of phages and bacteria. These co-adaptations have led to the development of multiple anti-phage defence systems in bacteria which modulate their susceptibility to be killed by phages at strain level. In this way, the study of the diversity and mechanisms of action of defence islands in bacterial pathogens represents crucial knowledge for improving rapid delivery of phage-based therapeutics. The proposed work aims to deeply characterize the anti-phage defences in an emerging human pathogen, antibiotic resistant Klebsiella pneumoniae, (according to Infectious Disease Society of America, one of the most dangerous worldwide disseminated pathogen, ESKAPE group composed by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) to provide the strategy to discover and classify phage counter-defences for an optimal design of phage therapy. To develop the project is necessary to characterize of the population genetics of K. pneumoniae to understand the distribution and diversity of anti-phage defence islands. The project was developed from 01-May-2019 to 31-August-2019 at Dr. German Bou laboratory (INIBIC, Spain). His extensive experience in clinical microbiology allowed to quickly stablish the protocols and to access to a collection of 334 carbapenem-resistant Enterobacteria and their genomic sequences. The project found effective phages against K. pneumoniae high risk clone (Kp3380). The isolated phages present different susceptibility patterns in close and distant related strains, allowing to design a future research line to unravel the genetic mechanisms behind anti-phage defence in K. pneumoniae. The study of K. pneumoniae pan-genome will allow to understand the antimicrobial resistance mechanisms and the genetic basis of anti-phage defences. This research line will continue with a close collaboration between Dr. Germán Bou and Prof. Martin Polz, who is a world expert in the ecology and evolution of environmental microbiology, in order to discover the genetic mechanisms of pathogens in order to improve clinical decisions to maximize the efficacy of antibiotic and phage therapeutics. This project will open a new field for the treatment of MDR infections by a tailor-phage strategy

Data: CORDIS, © European Union