Isolation, identification and genome analysis of a new Escherichia coli phage XH12 and enhancement of antibacterial activity of its lysozyme by chimeric cationic peptides

Antibiotics are no longer adequate to address the threat of antibiotic resistance, especially Pseudomonas aeruginosa , Acinetobacter baumannii , Escherichia coli and other gram-negative pathogens, which pose a serious threat to human health worldwide. The antibiotic resistance pandemic requires the search for new antimicrobials as alternatives that are effective and less prone to resistance. Phages and its lysozyme become an attractive alternative to currently available antibiotics. However, gram-negative bacteria have outer membrane that acts as a strong barrier, so lysozymes are often used in combination with outer membrane permeator, or are modified to overcome the outer membrane barrier. To combat drug-resistant E. coli , in this study, we used multidrug-resistant E. coli eco-3 as host bacteria, a lytic phage XH12 was isolated from sewages, phage XH12 can lyse about 81% (30/37) of E. coli strains tested. The biological characteristics and genome of phage XH12 were analyzed, and we found that lysozyme Lys12 encoded by phage XH12 combined with ethylenediaminetetraacetic acid (EDTA) had antibacterial activity against E. coli . Two fusion lysozymes were obtained by fusing different amounts of cationic amino acid polypeptides with the C-terminal of Lys12. The fusion lysozymes could improve the antibacterial activity against E. coli from extracellular space. The study of phage XH12 and its lysozyme will provide basic information for further study of the treatment of multidrug-resistant E. coli infection.