# Antibacterial Activity of Bacteriophage Lytic Enzyme Ply900

## TL;DR

This study shows that the enzyme Ply900 can effectively kill Streptococcus bacteria in lab and mouse experiments, offering a potential alternative to antibiotics.

## Contribution

Ply900 is a novel bacteriophage lytic enzyme with broad antibacterial activity and no induced resistance in vivo.

## Key findings

- Ply900 effectively kills multiple Streptococcus serotypes and Staphylococcus aureus in vitro.
- In mice, Ply900 treatment improved survival rates against S. suis serotype 2 infections.
- Ply900's mechanism involves synergistic domain activity without resistance development.

## Abstract

This study identified a novel bacteriophage lytic enzyme, Ply900, which exhibits strong lytic activity against various serotypes of Streptococcus in vitro. In the in vivo experiments, this enzyme exhibits protective effects in the mice challenged with lethal doses of Streptococcus suis (S. suis) serotype 2. The experimental results of this study suggest that lysozyme Ply900 can be classified as a potential antibacterial agent capable of effectively treating S. suis type 2 infections, demonstrating significant potential as an alternative to antibiotics.

S. suis is a prominent zoonotic pathogen responsible for diseases such as arthritis in piglets, swine septicemia, and meningitis. The emergence of multi-drug resistance (MDR) underscores the urgent need for the development of novel antibacterial strategies. In this context, a systematic evaluation of the antibacterial potential of the bacteriophage lytic enzyme Ply900 was conducted in this study, along with an analysis of its domain functions and an in vivo study of its therapeutic dynamics. Ply900 exhibits potent in vitro lytic activity against multiple bacteria, including Streptococcus suis, Streptococcus agalactiae, and Staphylococcus aureus. Notably, it possesses broad biochemical stability, with tolerance to diverse environmental conditions. In a mouse model of S. suis serotype 2 SC19 infection, both the direct Ply900 treatment group and the triple therapy group achieved effective eradication of S. suis, with markedly improved survival rates. The remaining bacteria remained susceptible to Ply900, with no evidence of induced resistance development. Mechanistic analysis revealed that the SH3B domain of Ply900 enhances targeted cleavage efficiency by binding synergistically to peptidoglycan with the CHAP domain, with CYS-34, HIS-59, and ASP-28 serving as key amino acid sites for Ply900’s cleavage activity. Collectively, these findings lay the foundation for the potential dual applications of the lysin Ply900, both in the clinical treatment of S. suis infections and in the prevention and control of these pathogenic bacteria in livestock farming.