近年来,肺炎克雷伯菌多重耐药(MDR)菌株已在全球范围内传播,负责医院感染的发生和严重程度。NDM-1-kp,产生VIM-1碳青霉烯酶的分离株以及产生广谱β内酰胺酶(ESBL)的分离株以及产酸克雷伯菌菌株已成为新兴的病原体。由于抗生素耐药性问题日益严重,噬菌体疗法可能是对抗这种多药耐药克雷伯菌菌株的潜在替代方法。这里,我们介绍了对肺炎克雷伯菌有活性的噬菌体的分离和生物学的长期研究结果,以及K.oxytoca菌株。我们评估了生物学特性,形态学,宿主特异性,裂解谱和这些噬菌体对化学试剂的敏感性,以及它们的生命周期参数,如吸附,潜伏期,和突发大小。我们指定的噬菌体,vB_KpnM-52N(Kpn52N)和VB_KpnM-53N(Kpn53N),在测试的克雷伯菌菌株中表现出相对较宽的裂解谱,高突发大小,吸附率和稳定性,这使得它们有希望用于治疗目的。我们还检查了从我们的历史收藏中选择的克雷伯菌噬菌体。值得注意的是,近60年前分离出的一种噬菌体成功用于一名新生儿的化脓性脑脊髓膜炎,至今仍保持着裂解活性。确定并分析所选噬菌体的基因组序列。测序基因组的噬菌体属于Slopekvirus和角达病毒属,在家庭水平上与T4相关的一组噬菌体。他们分享T4的几个特点,使它们适合抗菌治疗:强制溶解的生活方式,缺乏已知毒力或抗生素抗性基因的同源物,和一系列酶在感染时降解宿主DNA。
In recent years, multidrug-resistant (MDR) strains of Klebsiella pneumoniae have spread globally, being responsible for the occurrence and severity of nosocomial infections. The NDM-1-kp, VIM-1 carbapenemase-producing isolates as well as extended-spectrum beta lactamase-producing (ESBL) isolates along with Klebsiella oxytoca strains have become emerging pathogens. Due to the growing problem of antibiotic resistance, bacteriophage therapy may be a potential alternative to combat such multidrug-resistant Klebsiella strains. Here, we present the results of a long-term study on the isolation and biology of bacteriophages active against K. pneumoniae, as well as K. oxytoca strains. We evaluated biological properties, morphology, host specificity, lytic spectrum and sensitivity of these phages to chemical agents along with their life cycle parameters such as adsorption, latent period, and burst size. Phages designated by us, vB_KpnM-52N (Kpn52N) and VB_KpnM-53N (Kpn53N), demonstrated relatively broad lytic spectra among tested Klebsiella strains, high burst size, adsorption rates and stability, which makes them promising candidates for therapeutic purposes. We also examined selected Klebsiella phages from our historical collection. Notably, one phage isolated nearly 60 years ago was successfully used in purulent cerebrospinal meningitis in a new-born and has maintained lytic activity to this day. Genomic sequences of selected phages were determined and analyzed. The phages of the sequenced genomes belong to the Slopekvirus and Jiaodavirus genus, a group of phages related to T4 at the family level. They share several features of T4 making them suitable for antibacterial therapies: the obligatorily lytic lifestyle, a lack of homologs of known virulence or antibiotic resistance genes, and a battery of enzymes degrading host DNA at infection.