Identification of a novel broad-spectrum endolysin, Ply0643, with high antibacterial activity in mouse models of streptococcal bacteriaemia and mastitis

• Published in: Research in veterinary science 2022-03, Vol.143, p.41-49
• Main Authors: Liu, Guangjin, Zhang, Shiyu, Gao, Tingting, Mao, Zhao, Shen, Yanling, Pan, Zihao, Guo, Changming, Yu, Yong, Yao, Huochun
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-Bacterial Agents - therapeutic use; Antibacterial activity; Antibacterial agents; Antibiotics; Antimicrobial agents; Bacteremia - drug therapy; Bacteriaemia; Bacterial infections; Bactericidal activity; Cloning; Drug resistance; Endolysin; Endopeptidases - therapeutic use; Enzymatic activity; Enzyme activity; Enzymes; Female; Infections; Mammary gland; Mammary glands; Mastitis; Mastitis - drug therapy; Mice; Molecular weight; Multidrug resistance; Pathogens; Peptides; pH effects; Phages; Proteins; Strains (organisms); Streptococcal Infections - drug therapy; Streptococcus; Streptococcus agalactiae; Streptococcus infections; Streptococcus suis; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2021.12.014

Streptococcal infections are very common in humans and animals, and they are usually treated with antibiotics. Multidrug-resistant Streptococcus strains have continuously emerged in recent years, prompting the search for alternatives to antibiotics. The use of endolysins encoded by phages has presented a promising alternative approach to treatment. In this study, a novel prophage endolysin, Ply0643, was identified from the prophage S. a 04. At an optimal concentration (30 μg/mL), rPly0643 exhibited broad and strong lysosomal enzyme activity against 66 Streptococcus strains from different sources while also maintaining high lytic activity over a wide pH range (pH 6–10) and a broad range of temperatures (28 °C–45 °C). Two in vivo treatments of rPly0643 (total 0.8 mg/mouse) significantly protected mice (80%) from lethal bacteriaemia with Streptococcus suis, and single treatments of rPly0643 (0.1 mg/gland) significantly reduced Streptococcus agalactiae concentrations and inflammation in murine mammary glands. These findings collectively demonstrate that Ply0643 exhibits good bactericidal activity both in vitro and in vivo, and therefore represents a useful antibacterial agent for combatting streptococcal infections. •Characterization of a novel endolysin Ply0643 with broad lysis against streptococcus spp.•Ply0643 plays a vital role in lysis activity depended on its full length.•rPly0643 has excellent therapeutic effects in the infected murine models of streptococcal bacteremia and mastitis.