How The Plague Microbe Gave Fleas A Chance
There’s a disease called Far East scarlet-like fever, or Izumi fever. It is caused by a bacterium called Yersinia pseudotuberculosis, which people can catch through contaminated food or water. Its symptoms are usually gentle: fever; stomach pains; nothing worse than a case of appendicitis.
But sometime between 1,500 and 6,400 years ago, this mild-mannered microbe started to change. One particular lineage picked up new genes, while silencing some of its existing ones. It gained the ability to spread via the bites of fleas, and started causing more lethal symptoms. It became what we now call Yersinia pestis—the cause of plague. Three times over, this microbe has swept the world in lethal epidemics including the infamous Black Death, which killed upwards of 75 million people in the 14th century. What a difference a few millennia of evolution can make.
Many scientists are now trying to understand the changes that transformed Y.pseudotuberculosis into its darker, deadlier offshoot. Joseph Hinnebusch from the National Institutes of Health is particularly intrigued by Y.pestis’s ability to hitchhike in fleas—an ability that its ancestor lacks, and one that assuredly contributed to its spread between humans and other mammals.
When Y.pseudotuberculosis infects a flea, it colonises the very end of the insect’s digestive system, where it can’t easily reach a new host. But Y.pestis does something different. Earlier this year, Hinnebusch found that this bacterium gained a gene that allowed it to grow further up the flea’s digestive tract. It also lost three genes that normally restrain it from growing into thick colonies called biofilms.
These four changes mean that Y.pestis forms thick colonies in a valve that connects its throat to its gut. These bacterial cities stop the flea from easily swallowing the blood that it sucks. As it tries, it dislodges the bacteria in the valve, and regurgitates these into whatever poor animal it has bitten. Thanks to changes in four genes, Y.pestis gained the ability to spread to new hosts by giving reflux to fleas.
Along the way, it also became less toxic. Y. pseudotuberculosis is milder to us, but it is surprisingly deadly to fleas. It causes diarrhoea, paralysis, and death in around 40 percent of the insects that suck it up. Hinnebusch, together with postdoc Iman Chouikha, has now discovered why. They fed fleas with blood containing narrower and narrower selections of Y. pseudotuberculosis proteins until they identified one that was consistently toxic.
It’s called urease, and it is partly encoded by a gene called UreD. When Hinnebusch and Chouikha deleted this gene, fleas could happily swallow Y. pseudotuberculosis without any problems. Urease breaks down a substance called urea and, in doing so, produces ammonia. Presumably, the build-up of ammonia is toxic to the flea. In fact, any urease protein will finish them off—even one from a bean plant proved lethal.
Y.pestis, unlike its close relative, can’t make urease. Thanks to a single mutation in its version of the UreD gene, it produces a half-formed and useless protein. By breaking this gene, it gained the ability to survive through a flea without killing it.
That was a crucial step. Fleas aren’t actually very efficient at transmitting Y.pestis. You need a lot of them to kickstart an outbreak of plague, and that can’t really happen if their microbes are killing 40 percent of them. Hinnebusch and Chouikha calculated that to transmit a Y.pestis strain that still made urease, you’d need more fleas than are commonly found on rodents. Without the mutation that broke UreD, the plague microbe would never have reached plague proportions.
References: Sun, Jarrett, Bosio & Hinnebusch. 2014. Retracing the Evolutionary Path that Led to Flea-Borne Transmission of Yersinia pestis. Cell Host and Microbe http://dx.doi.org/10.1016/j.chom.2014.04.003
Chouikha & Hinnebusch. 2014. Silencing urease: A key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route. http://dx.doi.org/10.1073/pnas.1413209111
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