Abstract
Extra-intestinal Escherichia coli express several virulence factors that increase their ability to colonize and survive in different localizations. The K1 capsular type is involved in several infections, including meningitis, urinary tract, and bloodstream infections. The aims of this work were to isolate, characterize, and assess the in vivo efficacy of phages targeting avian pathogenic E. coli (APEC) O18:K1, which shares many similarities with the human strains responsible for neonatal meningitis. Eleven phages were isolated against APEC O18:K1, and four of them presenting a narrow spectrum targeting E. coli K1 strains were further studied. The newly isolated phages vB_EcoS_K1-ULINTec2 were similar to the Siphoviridae family, and vB_EcoP_K1-ULINTec4, vB_EcoP_K1-ULINTec6, and vB_EcoP_K1-ULINTec7 to the Autographiviridae family. They are capsular type (K1) dependent and present several advantages characteristic of lytic phages, such as a short adsorption time and latent period. vB_EcoP_K1-ULINTec7 is able to target both K1 and K5 strains. This study shows that these phages replicate efficiently, both in vitro and in vivo in the Galleria mellonella model. Phage treatment increases the larvae survival rates, even though none of the phages were able to eliminate the bacterial load.
Highlights
Extra-intestinal Escherichia coli (ExPEC) is a pathotype that encompasses a great diversity of strains, and in which antibiotic resistance increases over the years
Among the 11 phages isolated against the avian strain O18:K1 (APEC 45), four had a narrow host spectrum specific to the capsular type K1: vB_EcoS_K1-ULINTec2, vB_EcoP_K1-ULINTec4, vB_EcoP_K1-ULINTec6, and vB_EcoP_K1-ULINTec7
This specificity represents an advantage for phage therapy, as it allows a precise targeting of specific bacteria, in contrast to antibiotic treatments, which affect a wider range of species, disrupting the microbiota
Summary
Extra-intestinal Escherichia coli (ExPEC) is a pathotype that encompasses a great diversity of strains, and in which antibiotic resistance increases over the years. ExPEC can be normal inhabitants of the gut microbiota but can express several virulence factors that allow them to colonize and survive in different localizations [1]. Among these factors, capsular type K1 is involved in ExPEC infections such as neonatal meningitis, urinary tract, and bloodstream infections [2,3,4,5]. The polysaccharidic structure of the K1 capsule allows E. coli to escape phagocytosis and survive and multiply outside the intestinal tract, as observed in neonatal meningitis, where it constitutes a determining virulence factor for the bacterial survival in the serum and for passage through the blood–brain barrier [6,7]. Resistance to ampicillin is quite common, and, extended-spectrum beta-lactamase and multi-drug resistant strains have been described in several studies [9,10,11,12]
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