PlyKp104, a Novel Phage Lysin for the Treatment of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Other Gram-Negative ESKAPE Pathogens

文献类型： 外文期刊

第一作者： Xu, Siyue

作者： Xu, Siyue;Zou, Geng;Zhang, Yue;Li, Jinquan;Euler, Chad W.;Raz, Assaf;Hernandez, Anaise;Serrano, Anna;Xu, Siyue;Andersson, Martin;Fischetti, Vincent A.;Li, Jinquan;Euler, Chad W.;Raz, Assaf;Hernandez, Anaise;Euler, Chad W.;Xu, Siyue;Andersson, Martin

作者机构：

关键词： bacteriophage; lysin; endolysin; antibiotic resistance; Klebsiella; Pseudomonas; ESKAPE; Gram negative; skin infection

期刊名称：ANTIMICROBIAL AGENTS AND CHEMOTHERAPY （ 影响因子：4.9； 五年影响因子：5.1 ）

ISSN： 0066-4804

年卷期： 2023 年 67 卷 5 期

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收录情况： SCI

摘要： Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal. We identified four putative lysins through bioinformatic analysis of Pseudomonas and Klebsiella phage genomes in the NCBI database and then expressed and tested their intrinsic lytic activity in vitro. The most active lysin, PlyKp104, exhibited >5-log killing against K. pneumoniae, P. aeruginosa, and other Gram-negative representatives of the multidrug-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, K. pneumonia, Acinetobacter baumannii, P. aeruginosa, and Enterobacter species) without further modification. PlyKp104 displayed rapid killing and high activity over a wide pH range and in high concentrations of salt and urea. Additionally, pulmonary surfactants and low concentrations of human serum did not inhibit PlyKp104 activity in vitro. PlyKp104 also significantly reduced drug-resistant K. pneumoniae >2 logs in a murine skin infection model after one treatment of the wound, suggesting that this lysin could be used as a topical antimicrobial against K. pneumoniae and other MDR Gram-negative infections. Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens.

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