Li Juan, Fang Qingqing, Luo Huan, Feng Yan, Feng Yu, Zong Zhiyong
Center of Infectious Diseases, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, China.
Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu, China.
BMC Microbiol. 2025 Jan 13;25(1):17. doi: 10.1186/s12866-024-03736-0.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a severe threat for human health and urgently needs new therapeutic approaches. Lytic bacteriophages (phages) are promising clinically viable therapeutic options against CRKP. We attempted to isolate lytic phages against CRKP of sequence type 11 and capsular type 64 (ST11-KL64), the predominant type in China.
We recovered a lytic phage from sewage collected at a wastewater treatment station in Sichuan province, China. We obtained the genome of this phage and found that it is distinct from all known phages with the highest overall DNA similarity (12.5%, 16% coverage and 78.4% identity) with phage vB_EcoM_PHB05 (accession no. NC_052652) in ICTV. This phage represents a novel viral genus of the subfamily Stephanstirmvirinae, for which we proposed "Sichuanvirus" as the genus name. This phage has a narrow host range lyse specific for KL64 Klebsiella. This phage has no genes referring to antimicrobial resistance, virulence, and lysogen and is stable to a wide range of pH and temperatures. We also obtained three bacterial mutants resistant to the phage and performed genome sequencing for them. We therefore discovered that the interruption of a capsular polysaccharide biosynthesis-related gene wcaJ by insertion sequences mediated the resistance to this phage.
We recovered and characterized a phage of "Sichuanvirus", a novel viral genus of subfamily Stephanstirmvirinae, which is suitable for phage therapy. The discovery of this phage expands the arsenal against CRKP.
耐碳青霉烯类肺炎克雷伯菌(CRKP)对人类健康构成严重威胁,迫切需要新的治疗方法。裂解性噬菌体是对抗CRKP有前景的临床可行治疗选择。我们试图分离针对序列型11和荚膜型64(ST11-KL64)的CRKP的裂解性噬菌体,这是中国的主要类型。
我们从中国四川省一个污水处理站收集的污水中分离出一种裂解性噬菌体。我们获得了该噬菌体的基因组,发现它与所有已知噬菌体不同,与国际病毒分类委员会(ICTV)中的噬菌体vB_EcoM_PHB05(登录号NC_052652)的总体DNA相似性最高(12.5%,覆盖率16%,同一性78.4%)。这种噬菌体代表了斯蒂芬斯特姆病毒亚科的一个新病毒属,我们提议将“Sichuanvirus”作为该属名。这种噬菌体具有狭窄的宿主范围,仅对KL64克雷伯菌有特异性裂解作用。这种噬菌体没有与抗微生物耐药性、毒力和溶原性相关的基因,并且在广泛的pH值和温度范围内稳定。我们还获得了三种对该噬菌体耐药的细菌突变体,并对它们进行了基因组测序。因此我们发现,插入序列介导的荚膜多糖生物合成相关基因wcaJ的中断介导了对这种噬菌体的耐药性。
我们分离并鉴定了一种“Sichuanvirus”噬菌体,它是斯蒂芬斯特姆病毒亚科的一个新病毒属,适用于噬菌体治疗。这种噬菌体的发现扩大了对抗CRKP的武器库。