VGJphi integration and excision mechanisms contribute to the genetic diversity of Vibrio cholerae epidemic strains.
Most strains of Vibrio cholerae are not pathogenic or cause only local outbreaks of gastroenteritis. Acquisition of the capacity to produce the cholera toxin results from a lysogenic conversion event due to a filamentous bacteriophage, CTX. Two V. cholerae tyrosine recombinases that normally serve to resolve chromosome dimers, XerC and XerD, promote CTX integration by directly recombining the ssDNA genome of the phage with the dimer resolution site of either or both V. cholerae chromosomes. This smart mechanism renders the process irreversible. Many other filamentous vibriophages seem to attach to chromosome dimer resolution sites and participate in the rapid and continuous evolution of toxigenic V. cholerae strains. We analyzed the molecular mechanism of integration of VGJ, a representative of the largest family of these phages. We found that XerC and XerD promote the integration of VGJ into a specific chromosome dimer resolution site, and that the dsDNA replicative form of the phage is recombined. We show that XerC and XerD can promote excision of the integrated prophage, and that this participates in the production of new extrachromosomal copies of the phage genome. We further show how hybrid molecules harboring the concatenated genomes of CTX and VGJ can be produced efficiently. Finally, we discuss how the integration and excision mechanisms of VGJ can explain the origin of recent epidemic V. cholerae strains.
Centre National de la Recherche Scientifique, Centre de Génétique Moléculaire, 91198 Gif-sur-Yvette, France.
Bhabatosh
B
Das
Julien
J
Bischerour
François-Xavier
FX
Barre
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001435:Bacteriophages / Q000502:physiology*; D002771:Cholera / Q000453:epidemiology / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics / Q000821:virology; D014644:Genetic Variation; D016679:Genome, Viral / Q000502:physiology; D006801:Humans; D014734:Vibrio cholerae / Q000235:genetics / Q000472:pathogenicity / Q000821:virology; D016662:Virus Integration / Q000502:physiology*
D001426:Bacterial Proteins
Mol Microbiol. 2004 Nov;54(4):935-47
15522078
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3004-9
15703294
Science. 1996 Jun 28;272(5270):1910-4
8658163
Gene. 1996 Feb 22;169(1):47-52
8635748
J Bacteriol. 2003 Dec;185(24):7231-40
14645284
Biochim Biophys Acta. 2003 Oct 15;1639(2):65-79
14559113
FEMS Microbiol Ecol. 2010 Dec;74(3):485-99
20662928
J Bacteriol. 2000 Oct;182(19):5530-8
10986258
Nature. 2002 Jun 6;417(6889):656-9
12050668
FEMS Microbiol Lett. 2008 Jul;284(2):225-30
18503544
Curr Opin Microbiol. 2003 Feb;6(1):35-42
12615217
Res Microbiol. 2005 Mar;156(2):245-55
15748991
Mol Cell. 2005 Jan 21;17(2):291-300
15664197
Microbiology (Reading). 2010 Jan;156(Pt 1):108-115
19833774
J Bacteriol. 2003 Oct;185(19):5685-96
13129939
Mol Microbiol. 2001 Jul;41(2):311-23
11489120
Plasmid. 2004 May;51(3):246-55
15109831
PLoS Genet. 2008 Sep 26;4(9):e1000201
18818731
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4377-82
20133778
Nature. 2010 Oct 21;467(7318):982-5
20944629
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1280-5
12529504
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5151-6
17360342
Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15442-7
19720995
Nature. 1959 May 30;183(4674):1533-4
13666809
Mol Cell. 2005 Aug 19;19(4):559-66
16109379