Walk among the Arctic ice and you’ll sometimes encounter distinctive patches of red snow. They’re caused by a species of bacteria called Colwellia psycherythraea. It’s a cold specialist – a cryophile – that can swim and grow in extreme subzero temperatures where most other bacteria would struggle to survive. Colwellia’s cold-tolerating genes allow it to thrive in the Arctic, but Barry Duplantis from the University of Victoria wants to use them in human medicine, as the basis of the next generation of anti-bacterial vaccines.
Colwellia’s fondness for cold comes at a price – it dies at temperatures that most other bacteria cope with easily. By shoving Colwellia genes into bacteria that cause human diseases, Duplantis managed to transfer this temperature sensitivity, creating strains that died at human body temperature. When he injected these heat-sensitive bacteria into mice, they perished, but not before alerting the immune system and triggering a defensive response that protected the mice against later assaults. The Colwellia genes transformed another species of bacteria from a cause of disease into a vaccine against it.
A similar approach has been used for decades to create vaccines against viral diseases, including polio and influenza. Usually, scientists grow a virus at low temperature until they can isolate a strain that’s sensitive to heat and can be used as a vaccine. For bacteria, scientists usually resort to a different tack – they grow the bug under special conditions, or deliberately mutate it, until they get a strain that’s not very good at causing disease. Duplantis wanted to see if the heat-sensitive approach would work for bacteria as well as it does for viruses.
Duplantis used nine Colwellia genes to create heat-sensitive strains of Francisella tularensis, a bacterium that is often passed from animals to humans and can cause the potentially fatal disease tularaemia. Each of the nine genes worked on its own to varying degrees.
While some of the resulting strains were eventually able to evolve temperature-resistant forms, five of them couldn’t. This makes sense when you consider that cryophiles have been evolving in cold climes for several million years. Their adaptations are deeply rooted in their genes and it ought to take a combination of several mutations to create heat-resistant versions.
Duplantis injected these sensitive strains into rats and mice at cool parts of their bodies, like their ears or the base of their tails. While normal strains soon spread to other organs, the heat-sensitive ones didn’t. One strain in particular protected the rodents against later infections by normal bacteria. Three weeks later, Duplantis exposed the mice to a dose of regular Franciscella so large that it would normally kill them within a few days. It didn’t – they became less ill and lost less weight than unvaccinated mice and weeks later, they were still alive and well.
It was a promising result, and Duplantis thinks that the same approach should work for other species of dangerous bacteria. Using genes borrowed from Colwellia, he has already managed to create heat-sensitive versions of Salmonella enterica, which causes food poisoning, and Mycobacterium smegmatis, a relative of the species that causes tuberculosis. Whether these strains can be used to vaccinate mice, or indeed humans, is another matter.
And creating vaccines isn’t the only use for heat-sensitive bacteria. The most dangerous species are very difficult to study, and scientists need to do so in expensive facilities with stringent safety measures. But that might change if we managed to engineer strains that die at low temperatures. If the bacteria die at human body temperature, the risks of accidental infection suddenly become very low. And as Duplantis says, that would reduce the need for “full physical containment.”
Reference: PNAS http://dx.doi.org/10.1073/pnas.1004119107
Image by Richard Finkelstein
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