Kinetics of Targeted Phage Rescue in a Mouse Model of Systemic Escherichia coli K1.

György Schneider,Nikolett Szentes,Marianna Horváth,Gergely Maróti,Zsolt Doffkay,Ágnes Dorn,Gábor Nagy,Gábor Rákhely,Alysia Cox,Tamás Kovács

doi:10.1155/2018/7569645

Abstract

Escherichia (E.) coli K1 strains remain common causative agents of neonatal sepsis and meningitis. We have isolated a lytic bacteriophage (ΦIK1) against E. coli strain IHE3034 and tested its specificity in vitro, as well as distribution and protective efficacy in vivo. The phage was shown to be specific to the K1 capsular polysaccharide. In the lethal murine model, a high level of protection was afforded by the phage with strict kinetics. A single dose of 1 x 108 phage particles administered 10 and 60 minutes following the bacterial challenge elicited 100 % and 95 % survival, respectively. No mice could be rescued if phage administration occurred 3 hours postinfection. Tissue distribution surveys in the surviving mice revealed that the spleen was the primary organ in which accumulation of active ΦIK1 phages could be detected two weeks after phage administration. These results suggest that bacteriophages have potential as therapeutic agents in the control of systemic infections.

Highlights

The number of bacterial septicemia cases has been on the rise worldwide, affecting more than a million Americans [1], of whom between 28 and 50 % die [2].After entering the body, survival and outcome of the hematogenous spread partially depends on the fitness and virulence factors of the invader
Bacteriophages against the newborn meningitis E. coli (NMEC) strain IHE3034 were isolated from raw sewage water harvested from the Tettye Forrashaz Treatment Plant located in Pecs-Pellerd, Hungary
Characterization of E. coli IHE3034 Bacteriophages Isolated from Sewage Water

Summary

Introduction

The number of bacterial septicemia cases has been on the rise worldwide, affecting more than a million Americans [1], of whom between 28 and 50 % die [2].After entering the body, survival and outcome of the hematogenous spread partially depends on the fitness and virulence factors of the invader. The K1 serotype of Escherichia (E.) coli is the leading causative agent of Gram-negative bacterial meningitis with significant mortality and morbidity in newborns worldwide [3]. Its pathogenesis and pathophysiology have been investigated mostly using two E. coli K1 isolates originally isolated from the cerebrospinal fluid (CSF) of neonates with sepsis and meningitis [4]. Serotypes of these strains (RS218 and IHE3034) are identical, O18:K1:H7 [4]. The K1 capsule identical to the capsule of Neisseria meningitides B is thought to be one of the most important virulence factors as it supports survival in the host [5]. No vaccination is available for this capsule type because of the molecular mimicry between the serogroup B capsule and the tissue antigen of neuron cell adhesion molecule [6]

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Conclusion