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World J Med Genet. May 27, 2014; 4(2): 27-33
Published online May 27, 2014. doi: 10.5496/wjmg.v4.i2.27
Acquisition and dissemination mechanisms of CTXΦ in Vibrio cholerae: New paradigm for dif residents
Bhabatosh Das, G Balakrish Nair, Rupak K Bhadra
Bhabatosh Das, G Balakrish Nair, Centre for Human Microbial Ecology, Translational Health Science and Technology Institute, Gurgaon 122 016, Haryana, India
Rupak K Bhadra, Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Author contributions: Das B, Nair GB and Bhadra RK solely contributed to this article.
Supported by Research in the Laboratory of Das B and Nair GB is funded in part by Department of Science Technology, No. SB/FT/LS-309/2012; Government of India (GOI) and the Department of Biotechnology, No. BT/MB/THSTI/HMC-SFC/2011; Research in the Laboratory of Bhadra RK is partly financially supported by Council of Scientific and Industrial Research, GOI and Indian Council of Medical Research, GOI
Correspondence to: Rupak K Bhadra, MSc, PhD, FAScT, Senior Principal Scientist, Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
Telephone: +91-33-24995840 Fax: +91-33-24735197
Received: December 26, 2013
Revised: April 10, 2014
Accepted: May 13, 2014
Published online: May 27, 2014

Vibrio cholerae (V. cholerae) genome is equipped with a number of integrative mobile genetic element (IMGE) like prophages, plasmids, transposons or genomic islands, which provides fitness factors that help the pathogen to survive in changing environmental conditions. Metagenomic analyses of clinical and environmental V. cholerae isolates revealed that dimer resolution sites (dif) harbor several structurally and functionally distinct IMGEs. All IMGEs present in the dif region exploit chromosomally encoded tyrosine recombinases, XerC and XerD, for integration. Integration takes place due to site-specific recombination between two specific DNA sequences; chromosomal sequence is called attB and IMGEs sequence is called attP. Different IMGEs present in the attP region have different attP structure but all of them are recognized by XerC and XerD enzymes and mediate either reversible or irreversible integration. Cholera toxin phage (CTXΦ), a lysogenic filamentous phage carrying the cholera toxin genes ctxAB, deserves special attention because it provides V. cholerae the crucial toxin and is always present in the dif region of all epidemic cholera isolates. Therefore, understanding the mechanisms of integration and dissemination of CTXΦ, genetic and ecological factors which support CTXΦ integration as well as production of virion from chromosomally integrated phage genome and interactions of CTXΦ with other genetic elements present in the genomes of V. cholerae is important for learning more about the biology of cholera pathogen.

Keywords: Vibrio cholerae, Cholera toxin phage, VGJΦ, Plasmids, Integrative mobile genetic element, XerC, XerD, Dimer resolution sites, attP, attB

Core tip: Integrative mobile genetic element (IMGE) like prophage, plasmid, transposon or genomic island plays crucial roles in the evolution of bacterial pathogens. The Vibrio cholerae (V. cholerae) genome harbors several such IMGEs, which provides virulence, antibiotic resistance and other fitness traits to cholera pathogen and directly contributes in its evolution. Cholera toxin encoding phage (CTXΦ) is a well characterized IMGE, found integrated in the dimer resolution sites of all epidemic V. cholerae strains and exploits host encoded XerC and XerD recombinases for its lysogenic conversion. In this review we discussed about integration and dissemination of CTXΦ and related IMGEs of V. cholerae.