Xia Feifei, Li Xin, Wang Bin, Gong Pengjuan, Xiao Feng, Yang Mei, Zhang Lei, Song Jun, Hu Liyuan, Cheng Mengjun, Sun Changjiang, Feng Xin, Lei Liancheng, Ouyang Songying, Liu Zhi-Jie, Li Xinwei, Gu Jingmin, Han Wenyu
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People's Republic of China.
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
Appl Environ Microbiol. 2015 Oct 16;82(1):87-94. doi: 10.1128/AEM.02581-15. Print 2016 Jan 1.
Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine.
肺炎是最常见的由金黄色葡萄球菌介导的疾病之一，由于多重耐药金黄色葡萄球菌尤其是耐甲氧西林金黄色葡萄球菌（MRSA）菌株的出现，这种感染的治疗正变得具有挑战性。据报道，源自噬菌体GH15的溶菌酶LysGH15对MRSA显示出高效和广泛的裂解谱，并且芹菜素可以显著减少金黄色葡萄球菌的α-溶血素。在本研究中，对LysGH15和芹菜素的联合疗法进行了体外和小鼠金黄色葡萄球菌肺炎模型的评估。体外未检测到LysGH15和芹菜素之间的相互不利影响。在动物实验中，联合疗法显示出比LysGH15或芹菜素单一疗法更有效的治疗效果（P<0.05）。接受联合疗法的小鼠在攻击后24小时内肺部的细菌载量为1.5个对数单位，而未受保护的小鼠或单独用芹菜素或LysGH15治疗的小鼠的细菌载量分别为10.2、4.7和2.6个对数单位。与其他组相比，联合疗法组显示出最佳的健康状态、最低的肺湿组织与干组织比例、肺中总蛋白和细胞量最少、病理表现最少以及细胞因子水平最低（P<0.05）。鉴于其更好的保护效果，LysGH15和芹菜素的联合疗法对治疗由MRSA引起的肺炎具有治疗潜力。本文报道了溶菌酶与源自中药的天然产物的联合疗法。
