Abstract:
Bacteriophage KL-2146 is a lytic virus isolated to infect Klebsiella pneumoniae BAA2146, a pathogen carrying the broad range antibiotic resistance gene New Delhi metallo-betalactamase-1 (NDM-1). Upon complete characterization, the virus is shown to belong to the Drexlerviridae family and is a member of the Webervirus genus located within the (formerly) T1-like cluster of phages. Its double-stranded (dsDNA) genome is 47,844 bp long and is predicted to have 74 protein-coding sequences (CDS). After challenging a variety of K. pneumoniae strains with phage KL-2146, grown on the NDM-1 positive strain BAA-2146, polyvalence was shown for a single antibiotic-sensitive strain, K. pneumoniae 13,883, with a very low initial infection efficiency in liquid culture. However, after one or more cycles of infection in K. pneumoniae 13,883, nearly 100% infection efficiency was achieved, while infection efficiency toward its original host, K. pneumoniae BAA-2146, was decreased. This change in host specificity is reversible upon re-infection of the NDM-1 positive strain (BAA-2146) using phages grown on the NDM-1 negative strain (13883). In biofilm infectivity experiments, the polyvalent nature of KL-2146 was demonstrated with the killing of both the multidrug-resistant K. pneumoniae BAA-2146 and drug-sensitive 13,883 in a multi-strain biofilm. The ability to infect an alternate, antibiotic-sensitive strain makes KL-2146 a useful model for studying phages infecting the NDM-1+ strain, K. pneumoniae BAA-2146. GRAPHICAL ABSTRACT.
摘要:
噬菌体KL-2146是一种分离的裂解病毒,可感染肺炎克雷伯菌BAA2146,这是一种携带广泛抗生素抗性基因新德里金属-β-淀粉酶-1(NDM-1)的病原体。在完成表征后,该病毒被证明属于Drexlerviridae家族,并且是位于(以前)T1样噬菌体簇内的Webervirus属的成员。它的双链(dsDNA)基因组长47,844bp,预计具有74个蛋白质编码序列(CDS)。在用在NDM-1阳性菌株BAA-2146上生长的噬菌体KL-2146挑战多种肺炎克雷伯菌菌株后,显示出单个抗生素敏感菌株的多价,肺炎克雷伯菌13,883,在液体培养中具有非常低的初始感染效率。然而,在肺炎克雷伯菌13,883感染一个或多个周期后,达到了近100%的感染效率,而对其原始宿主的感染效率,肺炎克雷伯菌BAA-2146下降。宿主特异性的这种变化在使用在NDM-1阴性菌株(13883)上生长的噬菌体再次感染NDM-1阳性菌株(BAA-2146)时是可逆的。在生物膜感染性实验中,KL-2146的多价性质在多菌株生物膜中同时杀死耐多药肺炎克雷伯菌BAA-2146和对药物敏感的13,883。感染替代者的能力,抗生素敏感菌株使KL-2146成为研究噬菌体感染NDM-1+菌株的有用模型,肺炎克雷伯菌BAA-2146。图形摘要。