High quality reference genomes for toxigenic and non-toxigenic Vibrio cholerae serogroup O139
toxigenic Vibrio cholerae of the O139 serogroup have been responsible for several large cholera epidemics in South Asia, and continue to be of clinical and historical significance today. This serogroup was initially feared to represent a new, emerging V. cholerae clone that would lead to an eighth cholera pandemic. However, these concerns were ultimately unfounded. The majority of clinically relevant V. cholerae O139 isolates are closely related to serogroup O1, biotype El Tor V. cholerae, and
... r V. cholerae, and comprise a single sublineage of the seventh pandemic El Tor lineage. Although related, these V. cholerae serogroups differ in several fundamental ways, in terms of their O-antigen, capsulation phenotype, and the genomic islands found on their chromosomes. Here, we present four complete, high-quality genomes for V. cholerae O139, obtained using long-read sequencing. Three of these sequences are from toxigenic V. cholerae, and one is from a bacterium which, although classified serologically as V. cholerae O139, lacks the CTXϕ bacteriophage and the ability to produce cholera toxin. We highlight fundamental genomic differences between these isolates, the V. cholerae O1 reference strain N16961, and the prototypical O139 strain MO10. These sequences are an important resource for the scientific community, and will improve greatly our ability to perform genomic analyses of non-O1 V. cholerae in the future. These genomes also offer new insights into the biology of a V. cholerae serogroup that, from a genomic perspective, is poorly understood. Vibrio cholerae is the aetiological agent of cholera, an acute, life-threatening diarrhoea which has spread worldwide in seven pandemics since the nineteenth century. V. cholerae is typically sub-classified into serogroups on the basis of its somatic O-antigen. Despite there being over 200 serogroups of V. cholerae 1,2 , only serogroup O1 has caused large scale epidemics historically 3 . Previous cholera pandemics have been caused by the classical biotype of V. cholerae O1, whereas the ongoing seventh pandemic, which began in the 1960s, is caused by the El Tor biotype of V. cholerae O1 3,4 . Non-O1 serogroups of V. cholerae do not appear to cause pandemics, though they may cause outbreaks of disease. This is exemplified by an outbreak in Sudan in 1968, caused by V. cholerae O37, which was subsequently found to be genetically related to pandemic V. cholerae O1 5-8 . In 1992, a V. cholerae clone of serogroup O139 caused a large cholera epidemic which spread rapidly across Bangladesh and India 9,10 . Due to the geographic location of the epidemic, this clone was given the name Vibrio cholerae O139 Bengal 10 (dubbed V. cholerae O139 hereafter). V. cholerae O139 caused substantial numbers of cholera cases in Southeast Asia in the early 1990s, and was anticipated to emerge as the aetiological agent of an eighth cholera pandemic 11-13 . However, rather than causing a pandemic, V. cholerae O139 was associated only with a low-level incidence of cholera cases after the initial 1992-93 epidemic, until a second large outbreak occurred in Bangladesh in the Spring of 2002 14 . The re-emergence of this serogroup renewed fear that an eighth pandemic of cholera was beginning, driven by V. cholerae O139 15 . Once again, V. cholerae O139 did not proceed to cause a cholera pandemic, and although it no longer appears to be causing epidemic cholera, this serogroup has continued to be isolated since 2002. Recently, non-toxigenic V. cholerae O139 have been isolated in Thailand 16 .