Natural Bred ε<sup>2</sup>-Phages Have an Improved Host Range and Virulence against Uropathogenic <i>Escherichia coli</i> over Their Ancestor Phages
Alternative treatments for <i>Escherichia coli</i> infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 <i>...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/ae8ac31bc865467e8a71d115bf0a1345 |
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| Sumario: | Alternative treatments for <i>Escherichia coli</i> infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 <i>E. coli</i> strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of <i>E. coli</i> strains. The bred phages, which we termed evolution-squared ε<sup>2</sup>-phages, of a mixture of <i>Myoviridae</i> have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, <i>Myoviridae</i> ε<sup>2</sup>-phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε<sup>2</sup>-phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε<sup>2</sup>-phages with the broadest host range reveals that they are mosaic intercrossings of 2–3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε<sup>2</sup>-phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε<sup>2</sup>-phages are remarkably more suitable than the wild-type phages for phage therapy. |
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