Li Ping, Ma Wenjie, Shen Jiayin, Zhou Xin
College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China.
Pharmaceutics. 2022 Sep 10;14(9):1916. doi: 10.3390/pharmaceutics14091916.
A novel temperate phage vB_KpnP_ZX1 was isolated from hospital sewage samples using the clinically derived K57-type as a host. Phage vB_KpnP_ZX1, encoding three lysogen genes, the repressor, anti-repressor, and integrase, is the fourth phage of the genus , family , ever discovered. Phage vB_KpnP_ZX1 did not show ideal bactericidal effect on 111-2, but TEM showed that the depolymerase Dep_ZX1 encoded on the short tail fiber protein has efficient capsule degradation activity. In vitro antibacterial results show that purified recombinant Dep_ZX1 can significantly prevent the formation of biofilm, degrade the formed biofilm, and improve the sensitivity of the bacteria in the biofilm to the antibiotics kanamycin, gentamicin, and streptomycin. Furthermore, the results of animal experiments show that 50 µg Dep_ZX1 can protect all 111-2-infected mice from death, whereas the control mice infected with the same dose of 111-2 all died. The degradation activity of Dep_ZX1 on capsular polysaccharide makes the bacteria weaken their resistance to immune cells, such as complement-mediated serum killing and phagocytosis, which are the key factors for its therapeutic action. In conclusion, Dep_ZX1 is a promising anti-virulence agent for the K57-type infection or biofilm diseases.
利用临床分离的K57型菌株作为宿主，从医院污水样本中分离出一种新型温和噬菌体vB_KpnP_ZX1。噬菌体vB_KpnP_ZX1编码三种溶原基因，即阻遏蛋白、抗阻遏蛋白和整合酶，是迄今发现的该属、该科的第四种噬菌体。噬菌体vB_KpnP_ZX1对111 - 2菌株未表现出理想的杀菌效果，但透射电镜显示，短尾纤维蛋白上编码的解聚酶Dep_ZX1具有高效的荚膜降解活性。体外抗菌结果表明，纯化的重组Dep_ZX1能显著抑制生物膜的形成，降解已形成的生物膜，并提高生物膜中细菌对卡那霉素、庆大霉素和链霉素等抗生素的敏感性。此外，动物实验结果表明，50 µg Dep_ZX1可使所有感染111 - 2菌株的小鼠免于死亡，而感染相同剂量111 - 2菌株的对照小鼠全部死亡。Dep_ZX1对荚膜多糖的降解活性使细菌对免疫细胞的抵抗力减弱，如补体介导的血清杀伤和吞噬作用，这是其发挥治疗作用的关键因素。综上所述，Dep_ZX1是一种有潜力的抗毒力因子，可用于治疗K57型菌株感染或生物膜疾病。
