LysZX4-NCA, a new endolysin with broad-spectrum antibacterial activity for topical treatment

• Published in: Virus research Vol. 340; p. 199296
• Main Authors: Li, Ping, Shen, Mangmang, Ma, Wenjie, Zhou, Xin, Shen, Jiayin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01.02.2024
• Subjects: Broad spectrum; Endolysin; Klebsiella pneumoniae; Outer membrane; Phage; Broad spectrum; Endolysin; Outer membrane; Klebsiella pneumoniae; Phage
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2023.199296

The prevalence of multidrug-resistant highly virulent Klebsiella pneumoniae (MDR-hvKP) requires the development of new therapeutic agents. Herein, a novel lytic phage vB_KpnS_ZX4 against MDR-hvKP was discovered in hospital sewage. Phage vB_KpnS_ZX4 had a short latent period (5 min) and a large burst size (230 PFU/cell). It can rapidly reduce the number of bacteria in vitro and improve survival rates of bacteremic mice in vivo from 0 to 80 % with a single injection of 10 PFU. LysZX4, an endolysin derived from vB_KpnS_ZX4, exhibits potent antimicrobial activity in vitro in combination with ethylenediaminetetraacetic acid (EDTA). The antimicrobial activity of LysZX4 was further enhanced by the fusion of KWKLFKI residues from cecropin A (LysZX4-NCA). In vitro antibacterial experiments showed that LysZX4-NCA exerts broad-spectrum antibacterial activity against clinical Gram-negative bacteria, including MDR-hvKP. Moreover, in the mouse model of MDR-hvKP skin infection, treatment with LysZX4-NCA resulted in a three-log reduction in bacterial burden on the skin compared to the control group. Therefore, the novel phages vB_KpnS_ZX4 and LysZX4-NCA are effective reagents for the treatment of systemic and local MDR-hvKP infections.