Cholera kills humans, nurtures insects
Pathogen-to-pathogen communication means cholera bacteria alter their behaviour depending on their host. Andrew Masterson reports.
Cholera is an extremely virulent bacterial disease that in severe cases can kill a human host within hours.
Research led by Layla Kamareddine of the Boston Children’s Hospital in the US, however, has found that if the same bacteria is introduced into an arthropod – in this case, a fruit fly – it does its damnedest to keep its host alive.
The finding is reported in the journal Nature Microbiology. Kamareddine and colleagues found that the bacteria – Vibrio cholerae – is able to alter its functioning in order to minimise its impact inside an insect.
The advantages of doing so are clear. The bacteria live in two markedly different environments – the human small intestine, and in water. In the latter, it has to colonise arthropod intestines and exoskeletons in order to survive.
It is in cholera’s best interest, then, to not kill its aquatic hosts. (Although many cases are mild to moderate, it could be argued, in contrast, that it is very much in cholera’s interest to kill its human hosts swiftly, maximising is own person-to-person transmission through explosive and watery diarrhoea.)
Using fruit flies as proxy aquatic hosts, Kamareddine’s team identified the mechanism by which V.cholerae is able not just to downplay its lethality in insects – but also induce the same behaviour in every other V.cholerae in the same intestine.
It does so using a mechanism called quorum sensing – a way of regulating its own gene expression that, according to some definitions, represents a collection of single-celled organisms suddenly functioning as a unified multicellular entity.
Quorum sensing emerges as a product of population density. Each bacterium produces a small molecule known as auto-inducer. When the number of auto-inducers in a given space exceeds a given threshold, gene transcription among the component bacteria changes.
The effect – found in many unicellular species – is assumed to allow the bacteria to adapt to the environment, through altered functions. In the case of V.cholerae inside a fruit fly, this assumes several forms. The bacteria consume fewer available nutrients, modify a biofilm made to protect against harsh conditions, and dramatically decrease virulence.
The researchers show that when living en masse inside arthropods, the bacteria reduce the production of compounds associated with biofilm creation, and stop production of the two toxins that induce fluid loss in humans.
The result is that the arthropods live longer, protecting and transporting their deadly cargo more effectively.
“Taken together,” the researchers write, “our studies suggest that a functional V. cholerae quorum sensing system benefits both host and pathogen by minimising the nutritional impact of infection.”