Li Xinxin, Chen Yibao, Wang Shuang, Duan Xiaochao, Zhang Fenqiang, Guo Aizhen, Tao Pan, Chen Huanchun, Li Xiangmin, Qian Ping
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, People's Republic of China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, People's Republic of China.
Infect Drug Resist. 2022 May 27;15:2689-2702. doi: 10.2147/IDR.S362743. eCollection 2022.
Methicillin-resistant (MRSA) is an important zoonotic pathogen worldwide. Infections due to MRSA are associated with higher mortality rates compared with methicillin-susceptible . Meanwhile, bacteriophages have been shown to overcome the emergence of MRSA.
Phage PHB22a, PHB25a, PHB38a, and PHB40a were isolated. Here, we evaluated the ability of a phage cocktail containing phages PHB22a, PHB25a, PHB38a, and PHB40a against MRSA S-18 strain in vivo and in vitro. Phage whole-genome sequencing, host-range determination, lytic activity, and biofilm clearance experiments were performed in vitro. larvae and a mouse systemic infection model to evaluate the efficacy of phage therapy in vivo.
The phage cocktail exhibited enhanced antibacterial and anti-biofilm effects compared to the single phage. Phage cocktail contained with Ca/Zn significantly reduced the number of viable bacteria (24-h or 48-h biofilm) by more than 0.81-log compared to the phage cocktail alone. Furthermore, we demonstrated that the addition of Ca and Zn phage cocktail could increase the survival rate of larvae infected with by 10% compared with phage cocktail alone. This was further confirmed in the mouse model, which showed a 2.64-log reduction of host bacteria S-18, when Ca and Zn were included in the cocktail compared with the phage cocktail alone.
Our results indicated that phage cocktail supplemented with Ca/Zn could effectively remove bacteria in biofilms and mice tissues infected with .
耐甲氧西林金黄色葡萄球菌（MRSA）是全球一种重要的人畜共患病原体。与甲氧西林敏感金黄色葡萄球菌相比，MRSA感染与更高的死亡率相关。同时，噬菌体已被证明能克服MRSA的出现。
分离出噬菌体PHB22a、PHB25a、PHB38a和PHB40a。在此，我们评估了含有噬菌体PHB22a、PHB25a、PHB38a和PHB40a的噬菌体鸡尾酒在体内和体外对MRSA S-18菌株的作用。在体外进行了噬菌体全基因组测序、宿主范围测定、裂解活性和生物膜清除实验。利用幼虫和小鼠全身感染模型评估噬菌体疗法在体内的疗效。
与单一噬菌体相比，噬菌体鸡尾酒表现出增强的抗菌和抗生物膜作用。与单独的噬菌体鸡尾酒相比，含有钙/锌的噬菌体鸡尾酒显著降低了活菌数量（24小时或48小时生物膜）超过0.81个对数。此外，我们证明，与单独的噬菌体鸡尾酒相比，添加钙和锌的噬菌体鸡尾酒可使感染MRSA的幼虫存活率提高10%。在小鼠模型中进一步得到证实，与单独的噬菌体鸡尾酒相比，当鸡尾酒中包含钙和锌时，宿主细菌S-18减少了2.64个对数。
我们的结果表明，补充钙/锌的噬菌体鸡尾酒可有效清除感染MRSA的生物膜和小鼠组织中的细菌。
