Phage Targeting Neonatal Meningitis E. coli K1 In Vitro in the Intestinal Microbiota of Pregnant Donors and Impact on Bacterial Populations

Int J Mol Sci. 2023 Jun 24;24(13):10580. doi: 10.3390/ijms241310580.

Abstract

Escherichia coli K1 is a leading cause of neonatal meningitis. The asymptomatic carriage of these strains in the maternal intestinal microbiota constitutes a risk of vertical transmission to the infant at birth. The aim of this work was to evaluate the efficacy of phage therapy against E. coli K1 in an intestinal environment and its impact on the intestinal microbiota. For this purpose, three independent experiments were conducted on the SHIME® system, the first one with only the phage vB_EcoP_K1_ULINTec4, the second experiment with only E. coli K1 and the last experiment with both E. coli K1 and the phage. Microbiota monitoring was performed using metagenetics, qPCR, SCFA analysis and the induction of AhR. The results showed that phage vB_EcoP_K1_ULINTec4, inoculated alone, was progressively cleared by the system and replicates in the presence of its host. E. coli K1 persisted in the microbiota but decreased in the presence of the phage. The impact on the microbiota was revealed to be donor dependent, and the bacterial populations were not dramatically affected by vB_K1_ULINTec4, either alone or with its host. In conclusion, these experiments showed that the phage was able to infect the E. coli K1 in the system but did not completely eliminate the bacterial load.

Keywords: Escherichia coli K1; Galleria mellonella; SHIME®; bacteriophage; intestinal microbiota; phage therapy.

MeSH terms

  • Bacteriophages*
  • Escherichia coli
  • Escherichia coli Infections* / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Infant
  • Infant, Newborn
  • Meningitis* / etiology
  • Podoviridae*
  • Pregnancy

Grants and funding

The project was financially supported by Wallonia in the framework of the call for projects organized by the BioWin competitiveness cluster.