title: Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants.
abstract: Pandemic V. cholerae strains in the O1 serogroup have 2 biotypes: classical and El Tor. The classical biotype strains of the sixth pandemic, which encode the classical type cholera toxin (CT), have been replaced by El Tor biotype strains of the seventh pandemic. The prototype El Tor strains that produce biotype-specific cholera toxin are being replaced by atypical El Tor variants that harbor classical cholera toxin. Atypical El Tor strains are categorized into 2 groups, Wave 2 and Wave 3 strains, based on genomic variations and the CTX phage that they harbor. Whole-genome analysis of V. cholerae strains in the seventh cholera pandemic has demonstrated gradual changes in the genome of prototype and atypical El Tor strains, indicating that atypical strains arose from the prototype strains by replacing the CTX phages. We examined the molecular mechanisms that effected the emergence of El Tor strains with classical cholera toxin-carrying phage. We isolated an intermediary V. cholerae strain that carried two different CTX phages that encode El Tor and classical cholera toxin, respectively. We show here that the intermediary strain can be converted into various Wave 2 strains and can act as the source of the novel mosaic CTX phages. These results imply that the Wave 2 and Wave 3 strains may have been generated from such intermediary strains in nature. Prototype El Tor strains can become Wave 3 strains by excision of CTX-1 and re-equipping with the new CTX phages. Our data suggest that inter-chromosomal recombination between 2 types of CTX phages is possible when a host bacterial cell is infected by multiple CTX phages. Our study also provides molecular insights into population changes in V. cholerae in the absence of significant changes to the genome but by replacement of the CTX prophage that they harbor.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea; Institute of Pharmacological Research, Hanyang University, Ansan, Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea; Institute of Pharmacological Research, Hanyang University, Ansan, Korea.
authors.forename: Dokyung
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea; Institute of Pharmacological Research, Hanyang University, Ansan, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea; Institute of Pharmacological Research, Hanyang University, Ansan, Korea.
authors.forename: Chan Hee
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
authors.forename: Jae Ouk
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
authors.forename: Manki
authors.initials: M
authors.lastname: Song
authors.affiliation: Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: Bhabatosh
authors.initials: B
authors.lastname: Das
authors.affiliation: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh; UCLA Fielding School of Public Health, Los Angeles, California, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America; Les Centres GHESKIO, Port-au-Prince, Haïti.
authors.forename: Jean William
authors.initials: JW
authors.lastname: Pape
authors.affiliation: Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Korea; Institute of Pharmacological Research, Hanyang University, Ansan, Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D015373:Bacterial Typing Techniques; D001435:Bacteriophages / Q000235:genetics / Q000302:isolation & purification*; D005075:Biological Evolution; D002771:Cholera / Q000382:microbiology*; D002772:Cholera Toxin / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D016679:Genome, Viral; D008969:Molecular Sequence Data; D039002:Prophages / Q000235:genetics / Q000302:isolation & purification*; D041241:Vibrio cholerae O1 / Q000145:classification* / Q000235:genetics / Q000821:virology*
chemical_list: D002772:Cholera Toxin