Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
Department of Bioengineering, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Int J Mol Sci. 2023 Feb 17;24(4):4038. doi: 10.3390/ijms24044038.
In order to address the upcoming crisis in the treatment of infections, caused by an increasing proportion of resistant isolates, new approaches to antimicrobial therapy must be developed. One approach would be to use (bacterio)phages and/or phage derivatives for therapy. In this study, we present a description of the first phage from the family. The vB_KpnP_Klyazma podovirus, which forms translucent halos around the plaques, was isolated from river water. The phage genome is composed of 82 open reading frames, which are divided into two clusters located on opposite strands. Phylogenetic analysis revealed that the phage belongs to the family, although its identity with the closest member of this family was not higher than 5%. The bacteriophage demonstrated lytic activity against all ( = 11) strains with the KL20 capsule type, but only the host strain was lysed effectively. The receptor-binding protein of the phage was identified as a polysaccharide depolymerase with a pectate lyase domain. The recombinant depolymerase protein showed concentration-dependent activity against all strains with the KL20 capsule type. The ability of a recombinant depolymerase to cleave bacterial capsular polysaccharides regardless of a phage's ability to successfully infect a particular strain holds promise for the possibility of using depolymerases in antimicrobial therapy, even though they only make bacteria sensitive to environmental factors, rather than killing them directly.
为了解决由于耐药分离株比例不断增加而导致的感染治疗即将出现的危机,必须开发新的抗菌治疗方法。一种方法是使用(细菌)噬菌体和/或噬菌体衍生物进行治疗。在这项研究中,我们介绍了来自 科的第一个噬菌体。该噬菌体为 vB_KpnP_Klyazma 微小噬菌体,在噬菌斑周围形成半透明晕圈,从河水分离得到。噬菌体基因组由 82 个开放阅读框组成,分为位于相反链上的两个簇。系统发育分析表明,噬菌体属于 科,尽管与该科最接近的成员的同一性不高于 5%。噬菌体对所有(=11)具有 KL20 荚膜类型的 菌株表现出裂解活性,但只有宿主菌株被有效裂解。噬菌体的受体结合蛋白被鉴定为具有果胶裂解酶结构域的多糖解聚酶。重组解聚酶蛋白对所有具有 KL20 荚膜类型的菌株表现出浓度依赖性活性。重组解聚酶能够切割细菌荚膜多糖,而不管噬菌体是否能够成功感染特定菌株,这为在抗菌治疗中使用解聚酶提供了可能性,即使它们只能使细菌对环境因素敏感,而不能直接杀死它们。