Intrinsic Antimicrobial Peptide Facilitates a New Broad-Spectrum Lysin LysP53 to Kill In Vitro and in a Mouse Burn Infection Model.

Antimicrobial resistance-related infections of Gram-negative pathogens pose a huge threat to global public health. Lysins, peptidoglycan hydrolases from bacteriophages, are expected as an alternative weapon against drug-resistant bacteria. In the present study, we report a new lysin LysP53 from phage 53. Bioinformatic analysis revealed that LysP53 contains a positively charged N-terminal region and a putative peptidase catalytic domain. In vitro biochemical experiments showed that LysP53 is active against multiple antibiotic-resistant Gram-negative bacteria, including , , , and , with a reduction of 5 logs in viable number after exposure to 100 μg/mL LysP53 for 1 h. Further studies showed that LysP53 contains a functional antimicrobial peptide, i.e., N-terminal 33 aa, with a comparable spectrum of activity to LysP53. In an -associated mouse model of burn infection, a single dose of 14 μg/mouse LysP53 (57.6 μM) showed higher decolonization efficacy than 4 μg/mouse minocycline- (874 μM; < 0.05) and buffer-treated groups ( <0.001), leading to a bacterial reduction of 3 logs. Our findings collectively establish that LysP53 could be a promising candidate in the treatment of topical infections caused by multiple Gram-negative pathogens.