Therapeutic Efficacy of LysGH15 against necrotising pneumonia Caused by Staphylococcus aureus in a rabbit model

Jingmin Gu ^* Bowei Zhang Liran Song Yongran Wang Meimei Zhang Chong Chen Hui Ning Li Wang Qiu Cao Xinwu Wang Wenyu Han Bin Wang Yalu Ji

• Jilin University, Changchun, China

Staphylococcus aureus (S. aureus) is one of the most important zoonotic pathogens and can be transmitted to humans through the meat diet routes, causing necrotising pneumonia. This study investigated the therapeutic effect of bacteriophage lysin LysGH15 on necrotising pneumonia in rabbit model caused by S. aureus. In the in vitro experiments, 50 μg/mL LysGH15 not only significantly reduced the viable count (approximately 3.24 × 10 6 CFU/g) of chicken meat stored at 4 °C for 48 h but also effectively reduced the viable count of chicken meat thawed at 4 °C and 30 °C, with reductions of approximately 1.42 × 10 6 CFU/g and 2.78 × 10 6 CFU/g, respectively. In the in vivo experiments, a single intranasal administration of 300 μg/rabbit increased the survival rate of rabbits to 60%. At 72 h postinfection, the number of bacteria in the lung tissues of the rabbits treated with LysGH15 was 7 × 10 4 CFU/g, which was significantly lower than that in the lung tissues of rabbits treated with PBS (7.76 × 10 6 CFU/g) or linezolid (6.38 × 10 5 CFU/g). In addition, LysGH15 treatment alleviated lung tissue damage in infected rabbits and significantly reduced the levels of Panton-Valentine leukocidin (PVL), alpha-toxin (Hla), and the cytokines IFN-γ, TNF-α, and IL-8 in their lung tissues, similar to those in rabbits treated with linezolid. These results suggest that LysGH15 has the potential to be used as a novel antimicrobial agent for the treatment of necrotising pneumonia caused by S. aureus.