Identification of Two Depolymerases From Phage IME205 and Their Antivirulent Functions on K47 Capsule of Klebsiella pneumoniae
Identification of Two Depolymerases From Phage IME205 and Their Antivirulent Functions on K47 Capsule of Klebsiella pneumoniae
复制标题
噬菌体IME205中两种解聚酶的鉴定及其对肺炎克雷伯菌K47荚膜的抗毒作用
DOI：
10.3389/fmicb.2020.00218
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发表时间：
2020-02-14
影响因子：
5.2
通讯作者：
Gao, Zhancheng
中科院分区：
文献类型：
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作者：
Liu, Yannan;Leung, Sharon Shui Yee;Gao, Zhancheng
耐碳青霉烯肺炎克雷伯菌（CRKP）对全球公共卫生构成重大威胁。本研究共收集到80株属于ST11的CRKP菌株，其中70%（56株）表达K47荚膜型。因此，预防和控制这些细菌引起的感染具有重要意义。胶囊解聚酶可以降解细菌表面多糖，降低其毒力，使细菌暴露于宿主免疫攻击。以前的研究已经证明了噬菌体编码的解聚合酶在体外和体内治疗CRKP感染的抗病毒药物的潜力。本研究对噬菌体IME205的两个胶囊解聚合酶（Dpo42和Dpo43）进行了表达和表征。尽管这两种解聚合酶作用于荚膜血清型K47的菌株，但它们对不同的菌株亚群有活性，这表明在该血清型中存在胶囊成分的细微差异。噬菌体IME205的宿主范围与Dpo42和Dpo43的特异性范围之和匹配。这两种酶在相对较宽的pH范围（Dpo42为pH 5.0-8.0， Dpo43为pH 4.0-8.0）和温度（20-70℃）下保持稳定的活性。此外，Dpo42和Dpo43均能使宿主细菌对血清补体的杀伤作用完全敏感，对红细胞无溶血活性。综上所述，胶囊解聚合酶是一种很有前途的抗CRKP感染的抗病毒药物。
Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a significant threat to global public health. In present research, a total of 80 CRKP strains belonging to ST11 were collected with 70% (56 of 80 isolates) expressing a K47 capsular type. Thus, it is significant to prevent and control infections caused by these bacteria. Capsule depolymerases could degrade bacterial surface polysaccharides to reduce their virulence and expose bacteria to host immune attack. Previous studies have demonstrated the potential of phage-encoded depolymerases as antivirulent agents in treating CRKP infections in vitro and in vivo. Here, two capsule depolymerases (Dpo42 and Dpo43) derived from phage IME205 were expressed and characterized. Although both depolymerases act on strains with a capsular serotype K47, they are active against different subsets of strains, indicating subtle differences in capsule composition that exist within this serotype. The host range of phage IME205 matched to the sum of specificity range of Dpo42 and Dpo43. These two enzymes maintained stable activity in a relatively broad range of pH levels (pH 5.0-8.0 for Dpo42 and pH 4.0-8.0 for Dpo43) and temperatures (20-70 degrees C). Besides, both Dpo42 and Dpo43 could make host bacteria fully susceptible to the killing effect of serum complement and display no hemolytic activity to erythrocytes. In summary, capsule depolymerases are promising antivirulent agents to combat CRKP infections.