The increasing emergence of multi-drug resistant Escherichia coli (E. coli) has become a global concern, primarily due to the limitation of antimicrobial treatment options. Phage therapy has been considered as a promising alternative for treating infections caused by multi-drug resistant E. coli. However, the application of phages as a promising antimicrobial agent is limited by their narrow host range and specificity. In this research, a recombinant T4-like phage, named WGqlae, has been obtained by changing the receptor specificity determinant region of gene 37, using a homologous recombination platform of T4-like phages established by our laboratory previously. The engineered phage WGqlae can lyse four additional hosts, comparing to its parental phages WG01 and QL01. WGqlae showed similar characteristics, including thermo and pH stability, optimal multiplicity of infection and one-step growth curve, to the donor phage QL01. In addition, sequencing results showed that gene 37 of recombinant phage WGqlae had genetically stable even after 20 generations. In planktonic test, phage WGqlae had significant antimicrobial effects on E. coli DE192 and DE205B. The optical density at 600 nm (OD600) of E. coli in phage WGqlae treating group was significantly lower than that of the control group (P < 0.01). Besides, phage WGqlae demonstrated an obvious inhibitory effect on the biofilm formation and the clearance of mature biofilms. Our study suggested that engineered phages may be promising candidates for future phage therapy applications against pathogenic E. coli in planktonic and biofilm forms.
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This study was supported by Grants from the National Natural Science Foundation of China (U1803109), Key research and development plan of Jiangsu province (BE2019304), National Key R&D Program of China (2018YFC1602500), the Central University Basic Scientific Research Fund-Animal pathogenic bacteria (KYZ201846) and Jiangsu modern agriculture (waterfowl) industrial technology system disease prevention and control innovation team (JATS222).
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The authors declare that they have no conflict of interest.
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Li, M., Shi, D., Li, Y. et al. Recombination of T4-like Phages and Its Activity against Pathogenic Escherichia coli in Planktonic and Biofilm Forms. Virol. Sin. 35, 651–661 (2020). https://doi.org/10.1007/s12250-020-00233-2
- T4-like phages
- Escherichia coli (E. coli)
- Homologous recombination