Shah M. FaruqueVincent C. TamNityananda ChowdhuryPornphan DiraphatMichelle DziejmanJohn F. HeidelbergJohn D. ClemensJohn J. MekalanosG. Balakrish NairInternational Centre for Diarrhoeal Disease Research BangladeshMahidol UniversityUniversity of Rochester School of Medicine and DentistryJ. Craig Venter InstituteInternational Vaccine Institute, SeoulHarvard Medical School2018-08-242018-08-242007-03-20Proceedings of the National Academy of Sciences of the United States of America. Vol.104, No.12 (2007), 5151-5156002784242-s2.0-34247587641https://repository.li.mahidol.ac.th/handle/20.500.14594/24229Cholera outbreaks in subSaharan African countries are caused by strains of the El Tor biotype of toxigenic Vibrio cholerae O1. The El Tor biotype is the causative agent of the current seventh cholera pandemic, whereas the classical biotype, which was associated with the sixth pandemic, is now extinct. Besides other genetic differences the CTX prophages encoding cholera toxin in the two biotypes of V. cholerae O1 have distinct repressor (rstR) genes. However, recent incidences of cholera in Mozambique were caused by an El Tor biotype V. cholerae O1 strain that, unusually, carries a classical type (CTX class) prophage. We conducted genomic analysis of the Mozambique strain and its CTX prophage together with chromosomal phage integration sites to understand the origin of this atypical strain and its evolutionary relationship with the true seventh pandemic strain. These analyses showed that the Mozambique strain carries two copies of CTXclass prophage located on the small chromosome in a tandem array that allows excision of the prophage, but the excised phage genome was deficient in replication and did not produce CTXclass virion. Comparative genomic microarray analysis revealed that the strain shares most of its genes with the typical El Tor strain N16961 but did not carry the TLC gene cluster, and RS1 sequence, adjacent to the CTX prophage. Our data are consistent with the Mozambique strain's having evolved from a progenitor similar to the seventh pandemic strain, involving multiple recombination events and suggest a model for origination of El Tor strains carrying the classical CTX prophage. © 2007 by The National Academy of Sciences of the USA.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMultidisciplinaryArticleSCOPUS10.1073/pnas.0700365104