Characterization and genome analysis of jumbo Escherichia phage UE-S1 and the antibacterial potential of its lysozyme against uropathogenic E. coli

对巨型大肠杆菌噬菌体UE-S1进行表征和基因组分析,并研究其溶菌酶对泌尿道致病性大肠杆菌的抗菌潜力。

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Abstract

BACKGROUND: Every year, millions of individuals worldwide are affected by urinary tract infections (UTIs), one of the most frequent bacterial infections. Uropathogenic Escherichia coli strains (UPEC) are the main cause of both complicated and uncomplicated UTIs. In addition, uropathogens are becoming progressively more resistant to commonly prescribed antibiotics. As a result, new strategies for the prevention and treatment of UTIs must be developed, and the use of bacteriophages and their enzymes are potential options to eliminate uropathogens from the urinary tract. RESULTS: The present study aimed to investigate the therapeutic efficiency of a UE-S1 phage and its lysozyme (LysUE1) against the MDR UPEC strain PSU-5266 (UE-17). The phage UE-S1 was isolated from sewage water and exhibited potent lytic activity against the UPEC strain. Biological characterization revealed that phage UE-S1 was stable over a wide range of temperatures (4 °C to 55 °C) and pH values (3 to 11) with an adsorption time of 15 min. The phage was able to lyse 31% (27/86) of the assessed bacterial strains and significantly inhibited bacterial growth without inducing phage resistance. TEM micrographs revealed that the phage had a Myoviridae morphology with an icosahedral head and long contractile tail. The genomic analysis of phage UE-S1 revealed that it is a jumbo phage with a 358 kb genome encoding 595 putative open reading frames. Among these, 108 predicted genes with putative functions were primarily associated with nucleotide metabolism, DNA replication, and recombination. Additionally, no antibiotic resistance, virulence, or lysogenic genes were detected. Phylogenetic analysis revealed that the new phage UE-S1 belongs to the genus Asteriusvirus. Moreover, the phage lysozyme LysUE1 was cloned, expressed, and purified. LysUE1 demonstrated lytic activity against Gram-negative (pathogenic E. coli strains) and Gram-positive (S. aureus) strains. CONCLUSION: Overall, the results indicated that phage UE-S1 and its lysozyme LysUE1 might be promising therapeutic agents for combating multidrug-resistant UPEC in UTIs.

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