Gao Mingming, Yu Xinting, Yang Cuiping, Mi Zhiqiang, Bai Changqing, Liu Chuanbin, Liu Huiying
Chinese PLA General Hospital, Beijing, 100853, China.
Mianyang Central Hospital, Mianyang, 621000, Sichuan, China.
Probiotics Antimicrob Proteins. 2025 Apr 29. doi: 10.1007/s12602-025-10543-0.
The rise in multidrug resistance and strong biofilm-forming ability of Staphylococcus aureus has led to significant public health concerns. Phage or phage-derived components, such as depolymerase or endolysin, have been considered as potential alternatives to antibiotics for combating antibiotic-resistant bacterial infections. In this study, we cloned and expressed a Staphylococcus aureus phage endolysin, LysP4, and identified its lytic activity. The bactericidal effect of LysP4 was more pronounced against planktonic cells in the logarithmic phase compared to those in the stationary phase. LysP4 reduces bacterial counts by 3 log CFU/mL in 60 min and about 2 log CFU/mL during the stationary phase. LysP4 exhibited optimal lytic activity at pH 5.0-7.0 and remained stable across a temperature range of 16 to 40 °C, with maximal activity observed at 37 °C. LysP4 effectively targets 31 of 38 Staphylococcus strains and successfully eliminates biofilms, reducing bacterial counts by 4 log CFU/mL when combined with vancomycin. Notably, LysP4 demonstrated no hemolytic effects on human red blood cells and no toxic effects on embryonic kidney cells or lung cancer cells. Based on these findings, we believe that LysP4 holds promise as a biological control agent against Staphylococcus infections.
金黄色葡萄球菌多重耐药性的增加及其强大的生物膜形成能力引发了重大的公共卫生问题。噬菌体或噬菌体衍生成分，如解聚酶或内溶素，已被视为对抗耐抗生素细菌感染的抗生素潜在替代品。在本研究中，我们克隆并表达了一种金黄色葡萄球菌噬菌体内溶素LysP4，并确定了其裂解活性。与稳定期的浮游细胞相比，LysP4对对数期浮游细胞的杀菌作用更明显。LysP4在60分钟内可使细菌数量减少3 log CFU/mL，在稳定期可减少约2 log CFU/mL。LysP4在pH 5.0 - 7.0时表现出最佳裂解活性，在16至40°C的温度范围内保持稳定，在37°C时观察到最大活性。LysP4有效地靶向38株金黄色葡萄球菌中的31株，并成功消除生物膜，与万古霉素联合使用时可使细菌数量减少4 log CFU/mL。值得注意的是，LysP4对人红细胞没有溶血作用，对胚胎肾细胞或肺癌细胞也没有毒性作用。基于这些发现，我们认为LysP4有望成为对抗金黄色葡萄球菌感染的生物控制剂。
