Phage targeting E. coli K1 in the intestinal microbiota of pregnant donors to fight neonatal meningitis

Escherichia coli capsular type K1 is a leading cause of human neonatal meningitis. The asymptomatic carriage of these strains in the maternal intestinal and vaginal microbiota constitutes a risk of vertical transmission to infant at birth. The aim of this work was to evaluate the efficacy of phage therapy against E. coli K1 in an intestinal environment. For this purpose, 3 independent experiments were conducted in triplicate on the SHIME® system (Simulator of Human Intestinal Microbial Ecosystem) inoculated with intestinal microbiota of 3 pregnant donors. After two weeks of stabilisation of the microbiota, experiments were conducted. In the first experiment, only the phage B_EcoP_K1_ULINTec4 was inoculated. In the second experiment, only E. coli O18:K1:H7 was inoculated and in the last experiment, E. coli was inoculated together with the phage. Phage and E. coli K1 concentrations were measured 3 times a week for 6 weeks. The results showed that phage K1_ULINTec4, when inoculated alone, was progressively cleared by the peristaltic system. In the presence of the target bacterium, after a decrease in the first days, the phage titers tended to stabilize between 4 and 5 log PFU/mL in both proximal and distal colons. Comparison of bacterial concentrations in experiments 2 and 3 showed that E. coli K1 persisted in the microbiota but with lower titers in presence of the phage. In conclusion, those experiments showed that the phage administered was able to affect the survival of E. coli K1 in the system but did not completely eliminate it. However, further research is needed to investigate the hypothesis that the phage K1_ULINTec4 is able to decrease the virulence of this strain.