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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Phage Biology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1454618
This article is part of the Research Topic Bacteriophages and Phage-Engineered Products for Antibacterial and Anticancer Applications View all 4 articles

The Antibacterial Activity of a Novel Highly Thermostable Endolysin, LysKP213, Against Gram-Negative Pathogens is Enhanced when Combined with Outer Membrane Permeabilizing Agents

Provisionally accepted
Dingjian Chu Dingjian Chu 1*Jing Lan Jing Lan 1*Lu Liang Lu Liang 2*Kaide Xia Kaide Xia 2Linlin Li Linlin Li 3*Lan Yang Lan Yang 3*Hongmei Liu Hongmei Liu 1*Tingting Zhang Tingting Zhang 1*
  • 1 Guizhou Medical University, Guiyang, Guizhou Province, China
  • 2 Maternal and Child Health Care Hospital of Guiyang City, Guiyang, China
  • 3 Fudan University, Shanghai, Shanghai Municipality, China

The final, formatted version of the article will be published soon.

    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℃, 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.

    Keywords: Phage, phage endolysin, Gram-Negative Bacteria, Polymyxin B, Cecropin A, Synergy

    Received: 25 Jun 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Chu, Lan, Liang, Xia, Li, Yang, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dingjian Chu, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
    Jing Lan, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
    Lu Liang, Maternal and Child Health Care Hospital of Guiyang City, Guiyang, China
    Linlin Li, Fudan University, Shanghai, 200433, Shanghai Municipality, China
    Lan Yang, Fudan University, Shanghai, 200433, Shanghai Municipality, China
    Hongmei Liu, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
    Tingting Zhang, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.