The antibacterial activity of a novel highly thermostable endolysin, LysKP213, against Gram-negative pathogens is enhanced when combined with outer membrane permeabilizing agents

• Published in: Frontiers in Microbiology
• Main Authors: Dingjian Chu, Jing Lan, Lu Liang, Kaide Xia, Linlin Li, Lan Yang, Hongmei Liu, Tingting Zhang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2024-10-01
• Subjects: phage; phage endolysin; Gram-negative bacteria; polymyxin B; cecropin A; synergy
• Online Access: https://www.frontiersin.org/articles/10.3389/fmicb.2024.1454618/full

Phages and phage-encoded lytic enzymes are promising antimicrobial agents. In this study, we report the isolation and identification of bacteriophage KP2025 from Klebsiella pneumoniae. Bioinformatics analysis of KP2025 revealed a putative endolysin, LysKP213, containing a T4-like_lys domain. Purified LysKP213 was found to be highly thermostable, retaining approximately 44.4% of its lytic activity after 20 h of incubation at 95°C, and approximately 57.5% residual activity after 30 min at 121°C. Furthermore, when administered in combination with polymyxin B or fused at the N-terminus with the antimicrobial peptide cecropin A (CecA), LysKP213 exhibited increased antibacterial activity against Gram-negative pathogens, including K. pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli, both in vitro and in vivo. These results indicated that LysKP213 is a highly thermostable endolysin that, when combined with or fused with an outer membrane permeabilizer, has enhanced antibacterial activity and is a candidate agent for the control of infections by Gram-negative pathogens.