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Filamentous phage integration requires the host recombinases XerC and XerD


Many bacteriophages and animal viruses integrate their genomes into the chromosomal DNA of their hosts as a method of promoting vertical transmission. Phages that integrate in a site-specific fashion encode an integrase enzyme that catalyses recombination between the phage and host genomes1,2. CTXφ is a filamentous bacteriophage that contains the genes encoding cholera toxin, the principal virulence factor of the diarrhoea-causing Gram-negative bacterium Vibrio cholerae3. CTXφ integrates into the V. cholerae genome in a site-specific manner4,5; however, the 6.9-kilobase (kb) CTXφ genome does not encode any protein with significant homology to known recombinases. Here we report that XerC and XerD, two chromosome-encoded recombinases that ordinarily function to resolve chromosome dimers at the dif recombination site6, are essential for CTXφ integration into the V. cholerae genome. The CTXφ integration site was found to overlap with the dif site of the larger of the two V. cholerae chromosomes. Examination of sequences of the integration sites of other filamentous phages indicates that the XerCD recombinases also mediate the integration of these phage genomes at dif-like sites in various bacterial species.

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Figure 1: Site-specific integration of CTXφ DNA into chrI of strain 2740-80.
Figure 4: Sequences of the chrI and chrII dif/attB regions.
Figure 2: Analysis of pCTX-Kn integration in 2740-80 derivatives. pCTX-Kn was introduced into several 2740-80 derivatives and total DNA was prepared from KnR transformants.
Figure 3: Filamentation in V. cholerae xer and dif mutants.
Figure 5: Alignment of dif-like chromosome junction sequences of various filamentous prophages.

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We thank L. Arciszewska, A. Camilli, A. Campbell, B. Davis, A. Kane, D. Raychaudhuri, M. Russel and A. Sonenshein for helpful suggestions, and E. Vimr for communication of unpublished observations. We are grateful to A. Kane and the New England Medical Center GRASP Center for the preparation of plates and media. We acknowledge the support of NIH, Howard Hughes Medical Institute and the Pew Foundation.

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Correspondence to Matthew K. Waldor.

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Huber, K., Waldor, M. Filamentous phage integration requires the host recombinases XerC and XerD. Nature 417, 656–659 (2002).

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