Posted on behalf of Marian Turner.
Next-generation sequencing means bacteria no longer have an option when it comes to location privacy. In the latest example of the use of genomics to track infections, a team of scientists have sequenced the genomes of 154 strains of Vibrio cholerae, the bacterium that causes cholera, to map its movement around the globe over the past 40 years.
Their study, published today in Nature, shows that the bacterial ancestor of current pandemic V. cholerae ‘El Tor’ strains originated in the Bay of Bengal sometime in the 1950s. From there, the bacteria have spread across the planet in three separate waves (pictured).
The scientists sequenced the genomes of historical bacterial strains from Africa, Asia, Europe and the Americas and identified defining genetic regions called single nucleotide polymorphisms, or SNPs. “As SNPs appear they can be inherited and used as a barcode for tracking,” says microbiologist Gordon Dougan from the Wellcome Trust Sanger Institute in Cambridge, UK, an author on the study. The team found that V. cholerae has spread by intercontinental movement, rather than just evolving from local strains.
“We regard the Bay of Bengal as the ultimate source of V. cholerae,” says Dougan. “The strains can then evolve further outside this region, but they eventually die out and are replaced by the next sweep from the Bay.”
The genome comparisons also revealed that V. cholerae’s antibiotic resistance has influenced how the bacteria spread. The scientists dated the bacteria’s acquisition of the SXT genetic region, which confers resistance to multiple antibiotics, to around 1982, coinciding with the start of the second wave of V. cholerae. Although antibiotics are only rarely used to treat cholera, the authors suspect that the bacteria are acquiring antibiotic resistance through a combination of direct and indirect exposure, and that resistance can trigger new transmission events.
The authors say their transmission maps could help tackle the disease in future outbreaks. Cholera is a gastrointestinal disease that causes watery diarrhea and infects 3-5 million people every year, killing more than 100,000 people. Although the infection is readily treatable with clean water and rehydration salts, its incidence is rising, usually in areas of poor sanitation, such as refugee camps or following disasters. An outbreak is currently sweeping Somalia and refugee camps in neighbouring Kenya and Ethiopia.
“If we know whether an outbreak has come from outside or arisen from a local source, we can decide better how to manage it,” says Dougan. He says this is especially important in areas in which cholera is not endemic, where early detection of cholera coming from an outside source might allow governments to introduce emergency vaccination programmes that could prevent the bacteria becoming established. Such tracking would require sequencing of the outbreak strain genome – but whole genome sequencing of bacteria is rapidly becoming commonplace.
This happened in Haiti following the 2010 earthquake. A paper published in mBio yesterday comparing the genomes of recent V. cholerae isolates from Nepal to the Haitian outbreak strains provides the most compelling evidence yet that cholera was brought to the country by Nepalese UN peacekeepers.
Although scientists suspected this transmission route soon after the Haitian outbreak arose, it took months for them to obtain the bacterial genomes they needed for this more definitive comparison. On the mBio blog, study author Paul Keim from the Translational Genomics Research Institute in Flagstaff, Arizona, says there is still only a small set of global V. cholerae genome sequences available for comparisons. “What this area needs is global cooperation and sharing of data and strains to be able to definitively identify sources,” he says.
Dougan hopes that their study will provide a framework within which this can occur. “We are now developing simple tools for scientists to use in the field so that we build a global map of cholera strains.”