Characterization of a T7-Like Lytic Bacteriophage of Klebsiella pneumoniae B5055: A Potential Therapeutic Agent

Characterization of a T7-Like Lytic Bacteriophage of Klebsiella pneumoniae B5055: A Potential Therapeutic Agent
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DOI:
10.1007/s00284-009-9430-y
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发表时间:
2009-09-01
影响因子:
2.6
通讯作者:
Chhibber, Sanjay
Chhibber, Sanjay
中科院分区:
生物学4区
文献类型:
--
作者:
Verma, Vivek;Harjai, Kusum;Chhibber, Sanjay

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抗菌或治疗用噬菌体的表征是强制性的,因为使用未表征的噬菌体被认为是前抗生素时代噬菌体治疗失败的主要原因之一。在本研究中,一个裂解噬菌体,KPO 1 K2,特异性肺炎克雷伯菌B5055,具有广泛的主机范围被选中进行表征。透射电镜观察表明,KPO 1 K2具有二十面体的五角形头部,顶到顶的头部直径约为39 nm。短的非收缩性尾部(10 nm)的存在表明其包含在家族短尾病毒科与T7样裂解噬菌体的名称。噬菌体生长周期的潜伏期为15分钟,爆发大小约为140个噬斑形成单位/感染细胞,以及基因组的42 kbps和结构蛋白模式的这种噬菌体进一步证实了它的T7样特征。噬菌体在4-11的宽pH范围内是稳定的,并且在37 A ° C下表现出最大活性。注射入小鼠后,在6小时,在血液以及肾脏和膀胱中观察到高噬菌体滴度,尽管肾脏和膀胱中的滴度高于血液。噬菌体在血液中的清除时间为36 h,而在肾脏和膀胱中的清除时间较长。我们建议使用这种特征性噬菌体KPO 1 K2作为预防/治疗剂,特别是用于治疗由肺炎克雷伯氏菌引起的导管相关UTI。
Characterization of bacteriophages to be used prophylactically or therapeutically is mandatory, as use of uncharacterized bacteriophages is considered as one of the major reasons of failure of phage therapy in preantibiotic era. In the present study, one lytic bacteriophage, KPO1K2, specific for Klebsiella pneumoniae B5055, with broad host range was selected for characterization. As shown by TEM, morphologically KPO1K2 possessed icosahedral head with pentagonal nature with apex to apex head diameter of about 39 nm. Presence of short noncontractile tail (10 nm) suggested its inclusion into family Podoviridae with a designation of T7-like lytic bacteriophage. The phage growth cycle with a latent period of 15 min and a burst size of approximately 140 plaque forming units per infected cell as well as a genome of 42 kbps and structural protein pattern of this bacteriophage further confirmed its T7-like characteristics. Phage was stable over a wide pH range of 4-11 and demonstrated maximum activity at 37A degrees C. After injection into mice, at 6 h, a high phage titer was seen in blood as well as in kidney and urinary bladder, though titers in kidney and urinary bladder were higher as compared to blood. Phage got cleared completely in 36 h from blood while from kidneys and urinary bladder its clearance was delayed. We propose the use of this characterized phage, KPO1K2, as a prophylactic/therapeutic agent especially for the treatment of catheter associated UTI caused by Klebsiella pneumoniae.