Scanning the Landscape of Genome Architecture of Non-O1 and Non-O139 Vibrio cholerae by Whole Genome Mapping Reveals Extensive Population Genetic Diversity

Abstract

Historically, cholera outbreaks have been linked to V. cholerae O1 serogroup strains or its derivatives of the O37 and O139 serogroups. A genomic study on the 2010 Haiti cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera and the lack of genomic sequences of such strains from around the world. Here we address these gaps by scanning a global collection of V. cholerae strains as a first step towards understanding the population genetic diversity and epidemic potential of non O1/non-O139 strains. Whole Genome Mapping (Optical Mapping) based bar coding produces a high resolution, ordered restriction map, depicting a complete view of the unique chromosomal architecture of an organism. To assess the genomic diversity of non-O1/non-O139 V. cholerae, we applied a Whole Genome Mapping strategy on a well-defined and geographically and temporally diverse strain collection, the Sakazaki serogroup type strains. Whole Genome Map data on 91 of the 206 serogroup type strains support the hypothesis that V. cholerae has an unprecedented genetic and genomic structural diversity. Interestingly, we discovered chromosomal fusions in two unusual strains that possess a single chromosome instead of the two chromosomes usually found in V. cholerae. We also found pervasive chromosomal rearrangements such as duplications and indels in many strains. The majority of Vibrio genome sequences currently in public databases are unfinished draft sequences. The Whole Genome Mapping approach presented here enables rapid screening of large strain collections to capture genomic complexities that would not have been otherwise revealed by unfinished draft genome sequencing and thus aids in assembling and finishing draft sequences of complex genomes. Furthermore, Whole Genome Mapping allows for prediction of novel V. cholerae non-O1/non-O139 strains that may have the potential to cause future cholera outbreaks.

Complete Genome Assemblies for Two Single-Chromosome Vibrio cholerae Isolates, Strains 1154-74 (Serogroup O49) and 10432-62 (Serogroup O27)

“…The finding of a single chromosome was independently verified by whole-genome mapping and pulsed-field gel electrophoresis of intact chromosomes of these two strains ( 3 ). Due to the nonstandard topology of these genomes, we reviewed OpGen Argus-generated in silico optical maps for orthogonal confirmation of the single-chromosome nature of each genome.…”

“…A genomic study on the 2010 Haitian cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera ( 2 ). In a recent study, we examined the genomic diversity of a large collection of V. cholerae strains belonging to different non-O1/non-0139 serogroups using whole-genome mapping ( 3 ). In that study, we found pervasive genetic and genomic structural diversity, including indels, duplications, and fusions of the usual two chromosomes.…”

Molecular tools in understanding the evolution of Vibrio cholerae

“…Next-generation sequencing merely produces draft or incomplete genomes, their higher contig numbers and varying qualities pose major challenges in genome assembly and closure ( Land et al, 2014 ). As a result, majority of the currently available Vibrio genome sequences are reported to be incomplete draft sequences ( Chapman et al, 2015 ). In contrary, the third generation (or ‘single molecule’) sequencing offers longer read lengths and potentially produces a finished or complete genome within a few hours.…”

Environmental Reservoirs of Vibrio cholerae: Challenges and Opportunities for Ocean-Color Remote Sensing

“…The Vibrio cholerae is the principal diarrheal human pathogen, causing acute intestinal infection with watery diarrhea. There are at least 200 serogroups of V. cholerae, with toxigenic serogroups of O1 and O139 involved in human epidemics [2,3]. In 2017, the cholera disease was reported to affect at least 47 countries worldwide, resulting in an estimated 2.9 million cases per year worldwide [4].…”