Tracking the movement of a deadly pathogen and biothreat agent

Melioidosis is a frequently fatal infectious disease caused by a bacterium (Burkholderia pseudomallei) found in soil in certain parts of the world. We have known about melioidosis for many years, but it’s only in the last 25 years that we have started to understand it better. So, what’s changed?

This blog is a crosspost from the Sanger Institute and is based on research published in Nature Microbiology.

Melioidosis was considered to be something of a medical curiosity and a rare tropical disease for many years, but recent figures are putting the record straight. An estimated 165,000 people develop this infection every year, around 89,000 of whom will die as a result.

There is also a great deal of information being accumulated to help people understand if they are at risk, and how to prevent getting infected. Maps are being regularly updated on the global whereabouts of the organism, with new data often being generated when diagnostic microbiology laboratories start providing facilities to culture people with fever for the first time. We now know that infection can result from bacteria being inoculated, ingested or inhaled, which implicates a wide range of human behaviour. This helps to shape guidelines on how to avoid getting a preventable disease.

The organism has also hit the headlines as a biothreat agent, meaning that the bacterium could be used by terrorists to infect people or contaminate the environment.

With the genomic revolution in full swing, we wanted to use this technology to see if genome sequencing of a global collection of isolates would allow us to plot its travel history. This is important, given its patchy global distribution. Our findings are consistent with the modern-day organism originating from Australia. From there, it seems to have been introduced just once into Asia, but after that the story changes – with evidence for repeated spread between countries bordered by the Mekong river, and between Malaysia and Singapore.

Transatlantic slave trade routes and sampling locations.
Transatlantic slave trade routes and sampling locations. Credit: Nature Microbiology. doi:10.1038/nmicrobiol.2016.263

From SE Asia, the organism was introduced into Africa and onwards to South America. The evolutionary clock of the bacterium can be used to estimate broad dates for these introductions. From this, we estimated that the organism was introduced into South America between 1682 and 1849, which overlaps with the height of the slave trade.

Another feature of the infection which has puzzled clinicians is that the way that people manifest infection (which organs are affected) can differ depending on where the bacterium was acquired, with a particular difference between Australia and SE Asia. For example, infection of the prostate and a particular type of brain involvement is well recognised in Australia, but not in SE Asia. An obvious explanation is that bacteria in the two regions have different gene sets in their genome, which lead to different patterns of interactions with humans.

We tested this possibility by looking for gene patterns, and found numerous examples of genes or gene variants that differed between bacteria from Australia and SE Asia. This included genes that encode virulence factors, such as those that allow bacteria to adhere to cells, and genes that promote survival inside of cells. This catalogue of genes has been shared with the scientific community to explore and mine.

Our findings provide some reassurance that the bacterium does not spread over long distances very often, although measures to prevent the transport of material contaminated with the organism are just as important as ever. Next steps are to complete targeted experimental work to confirm which of the gene differences found here relate to particular disease types in melioidosis. Our goal is to understand how we can modulate the disease process to improve patient outcome.

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