Studying bubonic plague at Northwestern

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Scenes from an earlier outbreak of bubonic plague
  • Scenes from an earlier outbreak of bubonic plague
The heyday of the bubonic plague ended about 400 years ago, but that doesn't mean the disease doesn't still exist. [Insert noise of impending doom here.] There are between 1,000 and 3,000 cases worldwide per year—a mere drop in the bucket compared to the 75 to 200 million during the Black Death of the Middle Ages—and scientists, in particular Wyndham Lathem, a professor of microbiology-immunology at Northwestern's Feinberg School of Medicine, are curious about what made the disease tick.

So Lathem and his colleagues are tracking the evolution of bubonic plague, in particular Yersinia pestis, the bacteria that causes it.

"We want to see if it's gotten more or less deadly over time," he says. "Was the strain from the 1350s anything close to what we have now, or was it an offshoot? So many people died. Maybe the old strain, the one that was superdeadly, doesn't exist."

By bacteria standards, Y. pestis is relatively young; it evolved between 1,500 and 20,000 years ago which, as Lathem points out, is a very short amount of time considering the first evidence of life on this planet appeared 3.6 billion years ago. Its closest ancestor is another bacteria called Yersinia pseudotuberculosis, which also makes humans sick, but something more like food poisoning than deadly bubonic plague. Lathem has been comparing the genomes of both bacteria to pinpoint the different genes that distinguish Y. pestis from its more mild predecessor.

Lathem
  • Lathem
He's also been comparing the genomes of Y. pestis in the U.S. and Europe with strains from China and Madagascar and with older versions of the bacteria that have been recovered from skeletons of people who died during earlier plagues.

Bubonic plague is spread by fleas and rats; the bacteria has to pass through a flea in order to cause bubonic plague. This is how it happens:

A flea takes its blood meal from a rat. The bacteria from the rat form a sticky mass, or biofilm, inside the flea which blocks blood from reaching the flea's stomach. The flea keeps eating, but its hunger isn't satiated. This makes the flea cranky and aggressive and more inclined to bite. When it bites, it regurgitates some of the bacteria back into the mammal. Once the bacteria gets inside the mammal, it can sense its environment and turns off the genes that cause the bacteria to form the biofilm. The bacteria are then able to spread to the lymph nodes to form buboes, which is why we call it the bubonic plague.

A sticky clump, highly magnified
  • Wyndham Lathem
  • A biofilm, highly magnified

If the flea happens to live on a rat that is in the presence of humans, it may bite and infect a human instead. That's why you don't see bubonic plague much in modern America except, Lathem says, in prairie dog towns in the southwest. Our standards of hygiene mean we don't really live in close proximity to rats anymore.

But what Lathem is really interested in is the sequence of genes in the Y. pestis bacteria and how they signal when to get the blood all sticky and when to turn the stickiness off. If he and his colleagues can understand how that mechanism works, Lathem reasons, they may be able to come up with new ways of treating the disease.

There's also the historical aspect.

"There were three big pandemics of the plague, in Roman times, during the Middle Ages, and during the 1800s," Lathem explains. "We have DNA taken from the grave sites of people who died during the Middle Ages. The people—and the bacteria—are long dead. But we can go in and use modern DNA sequencing to find out the genetic content. In theory, we could imagine how the gene worked.

"We can compare Gene X in the modern bacteria to Gene X in the older strains. We can infer how the strain has evolved over time."

Then, Lathem says, scientists can alter the genes of living bacteria so that they resemble the older strains, and see how they behave.

Eventually, Lathem hopes to assemble a timeline of how Y. pestis has evolved over time. "We want to put together when those changes occurred."

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