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φbO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic Clonal Group 258 clade II lineage

机译:φbO1E,一种新发现的针对大流行性克隆组258进化枝II血统的产碳青霉烯酶的肺炎克雷伯菌的溶菌噬菌体

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摘要

The pandemic dissemination of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) represents a major public health problem, given their extensive multidrug resistance profiles and primary role in causing healthcare-associated infections. This phenomenon has largely been contributed by strains of Clonal Group (CG) 258, mostly of clade II, which in some areas represent the majority of KPC-KP isolates. Here we have characterized a newly discovered lytic Podoviridae, named φBO1E, targeting KPC-KP strains of clade II lineage of CG258. Genomic sequencing revealed that φBO1E belongs to the Kp34virus genus (87% nucleotide identity to vB_KpnP_SU552A). ΦBO1E was stable over a broad pH and temperature range, exhibited strict specificity for K. pneumoniae strains of clade II of CG258, and was unable to establish lysogeny. In a Galleria mellonella infection model, φBO1E was able to protect larvae from death following infection with KPC-KP strains of clade II of CG258, including one colistin resistant strain characterized by a hypermucoviscous phenotype. To our best knowledge φBO1E is the first characterized lytic phage targeting K. pneumoniae strains of this pandemic clonal lineage. As such, it could be of potential interest to develop new agents for treatment of KPC-KP infections and for decolonization of subjects chronically colonized by these resistant superbugs.
机译:产生KPC碳青霉烯酶的肺炎克雷伯菌(Klebsiella pneumoniae)(KPC-KP)的大流行传播是一个主要的公共卫生问题,因为它们广泛的多药耐药性和在引起医疗相关感染中起主要作用。这种现象在很大程度上是由克隆群(CG)258菌株造成的,其中大部分是进化枝II,在某些地区代表了大多数KPC-KP分离株。在这里,我们表征了一种新发现的裂解性足病毒科,名为φBO1E,其针对CG258进化枝II谱系的KPC-KP菌株。基因组测序表明,φBO1E属于Kp34病毒属(与vB_KpnP_SU552A的核苷酸同一性为87%)。 ΦBO1E在很宽的pH和温度范围内稳定,对CG258进化枝II的肺炎克雷伯氏菌菌株表现出严格的特异性,并且无法建立溶源性。在Galleria mellonella感染模型中,ΦBO1E能够保护幼虫免于感染CG258进化枝II的KPC-KP菌株,包括一种以黏液黏液表型为特征的大肠粘菌素抗性菌株。据我们所知,φBO1E是针对这种大流行性克隆谱系的肺炎克雷伯菌菌株的第一个特征性裂解噬菌体。因此,开发新的药物来治疗KPC-KP感染和将这些抗性超级细菌长期定殖于受试者的非殖民化可能具有潜在的兴趣。

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