Genome_wide_Analysis_of_Vibrio_cholerae_Circulating_in_Bangladesh

Cholera is an ancient disease of great historical importance. Even with modern established treatments and preventative measures, the causative agent Vibrio cholerae continues to emerge as a dangerous pathogen. This is especially true in Southeast Asia where the yearly appearance of cholera cases follow predicted patterns or “seasons”.1,2 There have been seven acknowledged pandemics of cholera to date and the current seventh pandemic manifesting as three major overlapping waves from the Ganges Delta of the Bay of Bengal. If applied to Bangladesh WGS for cholera will reveal the population structure of V. cholerae isolates circulating this region, their relationship to source and site, drug resistance profiles, and elude to whether the vaccine could afford adequate protection against these strains. Moreover, mapping annual outbreaks of cholera in Bangladesh, will build infrastructure and expertise for diarrheal and other infectious disease surveillance and provide essential consultation services to the nation's water and sanitation sector. Identifying the most disease-prone regions in Bangladesh will allow the sector to best allocate its resources in order to effectively prevent cholera. V. cholerae samples for WGS sequencing have been collected from an ongoing cholera surveillance study organised by icddr,b since 2014 to date, comprising 22 different health facilities in all eight divisions across Bangladesh. All of the isolates in collection were taken from individuals suffering from acute watery diarrhoea, both hospitalized and outpatients, and some were derived from asymptomatic carriers. Clinical data such as age, sex, degree of disease severity, and co-infection with other enteric bacterial pathogens (ETEC, shigella spp., salmonella spp.) were also documented or tested for each cholera case. WGS data will be used to construct phylogenies to understand the evolutionary relationships between Bangladeshi isolates. In cases where detailed sample information or meta-data is available, we will use phylogeny alongside clinical, phenotypic, geographical or other meta-data to track and understand the global and regional spread of cholera. To determine the relatedness, study V. cholerae strains will be used to establish a local bacterial population framework and to unequivocally place these isolates into the phylogenetic context of V. cholerae isolated across the world. Single nucleotide polymorphism (SNP) will be used to study the population structure and classify the strains into different genotypes or haplotypes. We will look for SNPs in Bangladeshi V. cholerae strains isolated from patients with severe, moderate and mild disease. Strains will be identified as different sub-groups based on the SNP analysis, and the pathogenic outcome of these sub-groups in study participants with different genetic markers will be studied. Genome characteristics, core genome and accessory genome analysis, investigation of the virulence factors, prophages, genomic islands, integrative conjugative elements (ICEs), and antibiotic resistance gene analysis will be performed. Further laboratory experiments will be designed and carried out based on the findings on WGS data. This study will support a PhD that is being jointly supervised by Prof Qadri and Thomson. This data has been described in the following article [doi or ref] and its further analysis can be freely submitted for publication. For information on the proper use of data shared by the Wellcome Trust Sanger Institute (including information on acknowledgement), please see http://www.sanger.ac.uk/datasharing/