Few creatures in the course of human history have ever been as influential as the one that crawls and jumps and drinks blood in the lab of Viveka Vadyvaloo.

It hit the world stage in the sixth century, starting in Lower Egypt, traveling by ship to Constantinople, then into western Europe. It took about half a century to kill 100 million people, half the earth’s population.

Imago Mortis from Liber Chronicarum
Imago Mortis from Liber Chronicarum, 1493 (Hartmann-Schedel, Nuremberg)

Seven centuries later, it fanned out from the Crimean seaport of Caffa to revisit Constantinople and Sicily, from which it swept through Italy, France, Spain, England, Germany, Austria, and Hungary. One-third of Europe, about 25 million people, was wiped out.

In the 1860s, it was China and India’s turn. More than 12 million died.

This wholesale destruction came through what is generally referred to as The Plague, most often manifested as the bubonic plague named after the swollen buboes that form around infected lymph glands. The first outbreak was the Plague of Justinian, after the Roman emperor of the time. The second was the Black Death. The third is more prosaically called the Third Pandemic, and it was not until then that the bacteriologists Alexandre Yersin and Kitasato Shibasaburo figured out that it was caused by a bacterium now called Yersinia pestis.

But many crimes require an accomplice. Yersinia’s is an unwitting insect that has spread the disease so effectively, it heralded the Dark Ages and forced the reorganization of trade networks and social strata. Historian William Rosen notes that the first plague allowed the rise of the major European nations we know today, in large part because the Roman Empire’s demise “was hastened by the bite of a flea.”

Xenopsylla cheopis, the Oriental rat flea, has been the disease’s main carrier, or vector, by moving the bacteria from rodent to rodent, and even today, to the occasional human.

“It’s the flea where the disease actually persists,” says Vadyvaloo, 36, an assistant professor in the College of Veterinary Medicine and the first faculty hire in the new School for Global Animal Health. Working out of a modest lab in the Animal Disease Biotechnology Facility, she maintains a small colony of fleas, sustaining them on a diet of fresh blood. While she works with an ineffective, avirulent strain of the bacterium, she can study various aspects of its transmission by running it through her fleas.

Viveka Vadyvaloo
Viveka Vadyvaloo (Photo Robert Hubner)

Fleas pick up the Yersinia bacterium by feeding on infected rodents. In the past, these were often rats, which traveled by ship from port to port, helping the disease spread across the Mediterranean and through Europe. Now it’s in other rodents—prairie dogs, blacktailed squirrels, groundhogs—which is how it is lingering in rural pockets across the western United States.

When an infected rat or ferret dies, its fleas go off in search of another warm meal. When that meal is the blood of a human, that can be a problem. It’s particularly a problem when the bacterium has given the flea indigestion.

Vadyvaloo’s work, by sitting squarely at the human-animal interface, “fits our mission perfectly,” says Guy Palmer, director of the School for Global Animal Health.

She’s looking in particular at how, in many fleas, Yersinia forms a slimy biofilm that can block up the flea’s proventriculus, an organ that helps move food from the throat to the stomach. Hungry, the flea starts a desperate and frustrated feeding frenzy.

But wait, it gets nastier. Because the proventriculus is blocked, the flea can’t actually consume the blood it’s sucking up. So it coughs. Back into its host. And remember those Yersinia bacteria down in the proventriculus? Some of them go into the host as well.

“It takes only five bacteria to result in your death 48 hours later,” says Vadyvaloo. “It’s very quick, very lethal.”

If someone can find a way to stop this behavior, Yersinia will have a lot fewer frustrated, biting, coughing fleas to do its bidding. So Vadyvaloo is looking very closely at how that biofilm is formed.

Before coming to WSU earlier this year, she studied the molecular mechanism of the biofilm’s formation in the flea as a postdoc at Rocky Mountain Labs, an obscure but prestigious national facility across the Bitterroots in Hamilton, Montana. Her work included making a profile of how Yersinia’s genetic information is used to synthesize various products. It was the first gene expression profile of an arthropod-borne bacterial pathogen—a significant accomplishment when you consider that arthropods host 80 percent of the world’s vector-borne pathogens.

Now Vadyvaloo is focusing on small RNA molecules that may have an outsized influence on how genes are expressed to make proteins. She is thinking these so-called small, non-coding RNAs are needed to form the biofilm. If she can identify them, they could lead to the actual genes required to make biofilm—and a possible technique to stop it in the future.

flea under microscope
A slimy film (red) produced by the Plague’s bacterium keeps food from reaching a flea’s stomach, sending it on a feeding frenzy that helps spread the disease. (Courtesy BJ Hinnebusch, Rocky Mountain Labs, NIAID/NIH)