<p>Antibiotics are no longer adequate to address the threat of antibiotic resistance, especially in <i>Pseudomonas aeruginosa</i>, <i>Acinetobacter baumannii</i>, <i>Escherichia coli</i>, and other Gram-negative pathogens that pose a serious threat to human health worldwide. The antibiotic resistance pandemic has brought about a need to search for new antimicrobials as alternatives that are effective and less prone to resistance. Phages and their lysozymes have become an attractive alternative to currently available antibiotics. However, Gram-negative bacteria have an outer membrane that acts as a strong barrier, so lysozymes are often used in combination with an outer membrane permeator or are modified to overcome the outer membrane barrier. To combat drug-resistant <i>E. coli</i>, in this study, we used the multidrug-resistant <i>E. coli</i> isolate Eco-3 as a host to isolate a lytic phage, XH12, from sewage. Phage XH12 was found to lyse 81% (30/37) of the <i>E. coli</i> isolates tested. The biological characteristics and genome sequence of phage XH12 were analyzed, and we found that lysozyme lys12 encoded by phage XH12, when combined with ethylenediaminetetraacetic acid (EDTA), exhibited antibacterial activity against <i>E. coli</i>. Two modified lysozymes were obtained by fusing cationic amino acid polypeptides to the C-terminus of lys12. The fusion lysozymes increased the antibacterial activity against <i>E. coli</i> in the extracellular space. This study of phage XH12 and its lysozyme provides basic information for further study of the treatment of multidrug-resistant <i>E. coli</i> infections.</p>

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

  • Xuhao Hou,
  • Jiaqi Pu,
  • Yu Li,
  • Wenhai Xie,
  • Limei Zhang,
  • Hongkuan Deng

摘要

Antibiotics are no longer adequate to address the threat of antibiotic resistance, especially in Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and other Gram-negative pathogens that pose a serious threat to human health worldwide. The antibiotic resistance pandemic has brought about a need to search for new antimicrobials as alternatives that are effective and less prone to resistance. Phages and their lysozymes have become an attractive alternative to currently available antibiotics. However, Gram-negative bacteria have an outer membrane that acts as a strong barrier, so lysozymes are often used in combination with an outer membrane permeator or are modified to overcome the outer membrane barrier. To combat drug-resistant E. coli, in this study, we used the multidrug-resistant E. coli isolate Eco-3 as a host to isolate a lytic phage, XH12, from sewage. Phage XH12 was found to lyse 81% (30/37) of the E. coli isolates tested. The biological characteristics and genome sequence of phage XH12 were analyzed, and we found that lysozyme lys12 encoded by phage XH12, when combined with ethylenediaminetetraacetic acid (EDTA), exhibited antibacterial activity against E. coli. Two modified lysozymes were obtained by fusing cationic amino acid polypeptides to the C-terminus of lys12. The fusion lysozymes increased the antibacterial activity against E. coli in the extracellular space. This study of phage XH12 and its lysozyme provides basic information for further study of the treatment of multidrug-resistant E. coli infections.