Intrinsic Antimicrobial Peptide Facilitates a New Broad-Spectrum Lysin LysP53 to Kill <i>Acinetobacter baumannii</i> In Vitro and in a Mouse Burn Infection Model

Abstract

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 <i>Acinetobacter baumannii</i> 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 <i>A. baumannii</i>, <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, and <i>Escherichia coli</i>, with a reduction of 5 logs in viable <i>A. baumannii</i> 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 <i>A. baumannii</i>-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; <i>p</i> < 0.05) and buffer-treated groups (<i>p</i> <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.