Why is cholera the deadly disease that refuses to die?

Posted by Biome on 6th August 2014 - 1 Comment

In 1893, the English medical journalist, editor and campaigner Ernest Abraham Hart took to the pages of the New Review periodical to warn that cholera was coming. Six years later, the sixth global cholera pandemic broke out in India, where it killed more than 800,000 people, and persisted for more than a quarter of a century, bringing misery to the diverse climes of the Russian Empire, the Middle East, North Africa and Eastern Europe.

A Saudi isolate from the sixth pandemic is one of 274 Vibrio cholera genomes included in a new study published in BMC Genomics that seeks to understand how this bacterium, the causative agent of cholera, is so successful at spreading itself across geographical space and historical time.

To tackle this question, Robert Edwards from San Diego State University, USA, and colleagues from the USA, the Netherlands, Brazil and Nigeria sequenced the genomes of 39 strains with Ion Torrent semiconductor sequencing technology, and analyzed the data produced together with 235 previously published V. cholera genomes. The resultant data resource represented isolates collected from all six inhabited continents, with locales as disparate as Peru, Bangladesh, Australia and Tanzania, and from a time span stretching from 1910 to the present day.

Waves of pandemics and bursts of epidemics were apparent in the clustering of single-nucleotide polymorphism (SNP) genetic markers from each of the V. cholera genome sequences. Alongside SNPs, other features annotated in the genomic data were protein families, functional subsystems, and sequences belonging to phages.

To understand how these various genomic features contribute to V. choleraā€™s breadth of habitation, machine learning was used to consider how each characteristic related to metadata on the year, location and habitat that each isolate was sourced from. In other words, each genome could be classified according to its niche in the three dimensions of space, time and habitat – and the genomic features that correlated with each niche could then be determined.

Based on this machine learning analysis, the study concluded that at the heart of V. choleraā€™s adaptability to these diverse niches lay an arsenal of mobile genetic elements: not only phages, but also endogenous factors such as prophages, transposable elements and plasmids.

The discovery that these elements are the chief culprits of cholera outbreaks adds to a growing body of work in which mobile DNA is shown to rapidly equip pathogens with the means to evade the dual threats of host immunity and medication. Although perhaps unsurprising, given that these genetic elements are the fastest evolving components of the V. cholera pan-genome, it is nevertheless sobering to witness with such clarity the extent to which mobile DNA has shaped this pathogen, across vast swathes of space and time, to the detriment of human happiness.


Written by Naomi Attar (@naomiattar), Associate Editor for BMC Biology.


Research article

Comparative genomics of 274 Vibrio cholerae genomes reveals mobile functions structuring three niche dimensions

Dutilh BE, Thompson CC, Vicente ACP, Marin MA, Lee C, Silva GGZ, Schmieder R, Andrade BGN et al.
BMC Genomics 2014, 15:654

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