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

Cells. 2023 Jan 17;12(3):344. doi: 10.3390/cells12030344.

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.

Keywords: antibiotic resistance; bacteriophage; biofilm-forming potential; inflammatory infections; intestinal microflora.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Bacteriophages*
  • Biofilms
  • Escherichia coli
  • Humans
  • Phage Therapy*

Substances

  • Anti-Bacterial Agents

Grants and funding

This work is funded by the European Commission under Horizon 2020′s Marie Skłodowska Curie Actions COFUND scheme (Grant Agreement No. 712754) and by the Severo Ochoa program of the Spanish Ministry of Science and Competitiveness (SEV-2014-0425 (2015–2019). ET was supported by grants from the 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 (RTI2018-098573-B-100, PID2021-125801OB-100 and PDC2022-133577-I00), the CERCA program and AGAUR-Generalitat de Catalunya (2017SGR-1079), the European Regional Development Fund (FEDER), Catalan Cystic Fibrosis Federation, and Obra Social “La Caixa”. JA is thankful to Generalitat de Catalunya, for its financial support through the FI program (2021FI_B00118). BVA-J is thankful to La Caixa Foundation (ID 100010434) for its Ph.D. grant (LCF/BQ/DI20/11780040).