Department of Biochemistry and Biophysics, Texas A&M University, 2128 TAMU, College Station, TX 77843-2128, USA.
J Bacteriol. 2011 Oct;193(19):5300-13. doi: 10.1128/JB.05287-11. Epub 2011 Jul 29.
Within the Burkholderia cepacia complex, B. cenocepacia is the most common species associated with aggressive infections in the lungs of cystic fibrosis patients, causing disease that is often refractive to treatment by antibiotics. Phage therapy may be a potential alternative form of treatment for these infections. Here we describe the genome of the previously described therapeutic B. cenocepacia podophage BcepIL02 and its close relative, Bcep22. Phage Bcep22 was found to contain a circularly permuted genome of 63,882 bp containing 77 genes; BcepIL02 was found to be 62,714 bp and contains 76 predicted genes. Major virion-associated proteins were identified by proteomic analysis. We propose that these phages comprise the founding members of a novel podophage lineage, the Bcep22-like phages. Among the interesting features of these phages are a series of tandemly repeated putative tail fiber genes that are similar to each other and also to one or more such genes in the other phages. Both phages also contain an extremely large (ca. 4,600-amino-acid), virion-associated, multidomain protein that accounts for over 20% of the phages' coding capacity, is widely distributed among other bacterial and phage genomes, and may be involved in facilitating DNA entry in both phage and other mobile DNA elements. The phages, which were previously presumed to be virulent, show evidence of a temperate lifestyle but are apparently unable to form stable lysogens in their hosts. This ambiguity complicates determination of a phage lifestyle, a key consideration in the selection of therapeutic phages.
在伯克霍尔德氏菌复合群中,洋葱伯克霍尔德菌是与囊性纤维化患者肺部侵袭性感染最相关的常见物种,导致疾病通常对抗生素治疗有抗性。噬菌体治疗可能是这些感染的潜在替代治疗方法。在这里,我们描述了先前描述的治疗性洋葱伯克霍尔德菌噬菌体 BcepIL02 及其近亲 Bcep22 的基因组。发现噬菌体 Bcep22 含有一个 63882bp 的环状排列基因组,包含 77 个基因;BcepIL02 为 62714bp,包含 76 个预测基因。通过蛋白质组学分析鉴定了主要的病毒相关蛋白。我们提出,这些噬菌体构成了一个新的噬菌体谱系的创始成员,即 Bcep22 样噬菌体。这些噬菌体的有趣特征之一是一系列串联重复的假定尾丝基因,它们彼此相似,也与其他噬菌体中的一个或多个这样的基因相似。这两种噬菌体还含有一个非常大的(约 4600 个氨基酸)、与病毒体相关的、多结构域蛋白,占噬菌体编码能力的 20%以上,广泛分布于其他细菌和噬菌体基因组中,并且可能参与促进噬菌体和其他移动 DNA 元件中的 DNA 进入。这些噬菌体以前被认为是毒性的,显示出温和噬菌体生活方式的证据,但显然不能在其宿主中形成稳定的溶原菌。这种模棱两可使得确定噬菌体的生活方式变得复杂,这是选择治疗性噬菌体的关键考虑因素。