Molecular Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka-1212, Bangladesh.
Nature. 2010 Oct 21;467(7318):982-5. doi: 10.1038/nature09469. Epub 2010 Oct 13.
Bacterial chromosomes often carry integrated genetic elements (for example plasmids, transposons, prophages and islands) whose precise function and contribution to the evolutionary fitness of the host bacterium are unknown. The CTXφ prophage, which encodes cholera toxin in Vibrio cholerae, is known to be adjacent to a chromosomally integrated element of unknown function termed the toxin-linked cryptic (TLC). Here we report the characterization of a TLC-related element that corresponds to the genome of a satellite filamentous phage (TLC-Knφ1), which uses the morphogenesis genes of another filamentous phage (fs2φ) to form infectious TLC-Knφ1 phage particles. The TLC-Knφ1 phage genome carries a sequence similar to the dif recombination sequence, which functions in chromosome dimer resolution using XerC and XerD recombinases. The dif sequence is also exploited by lysogenic filamentous phages (for example CTXφ) for chromosomal integration of their genomes. Bacterial cells defective in the dimer resolution often show an aberrant filamentous cell morphology. We found that acquisition and chromosomal integration of the TLC-Knφ1 genome restored a perfect dif site and normal morphology to V. cholerae wild-type and mutant strains with dif(-) filamentation phenotypes. Furthermore, lysogeny of a dif(-) non-toxigenic V. cholerae with TLC-Knφ1 promoted its subsequent toxigenic conversion through integration of CTXφ into the restored dif site. These results reveal a remarkable level of cooperative interactions between multiple filamentous phages in the emergence of the bacterial pathogen that causes cholera.
细菌染色体通常携带整合的遗传元件（例如质粒、转座子、噬菌体和岛），其确切功能及其对宿主细菌进化适应性的贡献尚不清楚。CTXφ 噬菌体在霍乱弧菌中编码霍乱毒素，已知其紧邻一个功能未知的染色体整合元件，称为毒素连接隐（TLC）。在这里，我们报告了一个与 TLC 相关的元件的特征，该元件对应于卫星丝状噬菌体（TLC-Knφ1）的基因组，该噬菌体利用另一种丝状噬菌体（fs2φ）的形态发生基因形成感染性的 TLC-Knφ1 噬菌体颗粒。TLC-Knφ1 噬菌体基因组携带类似于 dif 重组序列的序列，该序列使用 XerC 和 XerD 重组酶在染色体二聚体分辨率中起作用。dif 序列也被溶原性丝状噬菌体（例如 CTXφ）用于其基因组在染色体上的整合。二聚体分辨率缺陷的细菌细胞通常表现出异常的丝状细胞形态。我们发现，TLC-Knφ1 基因组的获得和染色体整合恢复了 V. 霍乱弧菌野生型和 dif(-)丝状表型突变菌株的完美 dif 位点和正常形态。此外，TLC-Knφ1 溶原化的 dif(-)非产毒 V. 霍乱弧菌通过将 CTXφ 整合到恢复的 dif 位点，促进了其随后的产毒转化。这些结果揭示了多种丝状噬菌体之间在导致霍乱的细菌病原体出现过程中存在显著的协同相互作用。
