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

Abstract

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.