Accessing the In Vivo Efficiency of Clinically Isolated Phages against Uropathogenic and Invasive Biofilm-Forming Escherichia coli Strains for Phage Therapy

Author:

Sanmukh Swapnil Ganesh12ORCID,Admella Joana1ORCID,Moya-Andérico Laura1ORCID,Fehér Tamás2ORCID,Arévalo-Jaimes Betsy Verónica1ORCID,Blanco-Cabra Núria13,Torrents Eduard13ORCID

Affiliation:

1. Bacterial Infections: Antimicrobial Therapies Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac, 15-21, 08028 Barcelona, Spain

2. Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Eötvös Lóránd Research Network, H-6726 Szeged, Hungary

3. Microbiology Section, Department of Genetics, Microbiology, and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain

Abstract

Escherichia coli is one of the most common members of the intestinal microbiota. Many of its strains are associated with various inflammatory infections, including urinary or gut infections, especially when displaying antibiotic resistance or in patients with suppressed immune systems. According to recent reports, the biofilm-forming potential of E. coli is a crucial factor for its increased resistance against antibiotics. To overcome the limitations of using antibiotics against resistant E. coli strains, the world is turning once more towards bacteriophage therapy, which is becoming a promising candidate amongst the current personalized approaches to target different bacterial infections. Although matured and persistent biofilms pose a serious challenge to phage therapy, they can still become an effective alternative to antibiotic treatment. Here, we assess the efficiency of clinically isolated phages in phage therapy against representative clinical uropathogenic and invasive biofilm-forming E. coli strains. Our results demonstrate that irrespective of host specificity, bacteriophages producing clear plaques with a high burst size, and exhibiting depolymerizing activity, are good candidates against biofilm-producing E. coli pathogens as verified from our in vitro and in vivo experiments using Galleria mellonella where survival was significantly increased for phage-therapy-treated larvae.

Funder

European Commission under Horizon 2020′s Marie Skłodowska Curie Actions COFUND scheme

Severo Ochoa program of the Spanish Ministry of Science and Competitiveness

Ministerio de Economia, Industria y Competitividad (MINECO), and Agencia Estatal de Investigación (AEI), Spain, co-funded by Fondo Europeo de Desarrollo Regional (FEDER), European Union

CERCA program and AGAUR-Generalitat de Catalunya

European Regional Development Fund (FEDER), Catalan Cystic Fibrosis Federation, and Obra Social “La Caixa”

FI program

La Caixa Foundation

Ph.D. grant

Publisher

MDPI AG

Subject

General Medicine

Reference68 articles.

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