How Does the Plague Kill People?

This article was originally posted on RealClearScience.

Every year, about seven Americans come down with plague. Yes, that plague, the one known as Black Death and which wiped out about one-third of Europe’s population in the mid-1300s.

Actually, the U.S. is lucky. Plague is a much bigger problem in many developing countries. For instance, a single outbreak in Madagascar in December 2013 killed 39 people, and from 2000-2009, more than 10,000 people died in Congo from plague. The reason plague is still around is because it lives in rodents, such as rats and prairie dogs, and is transmitted to humans by fleas. It would be impractical, to say the least, to vaccinate or eradicate the world’s rodent community, so the next best thing is for doctors to be able to quickly identify patients infected with plague and to administer antibiotics.

People who are treated are far more likely to survive than those who are not (~90% survival vs. ~30% survival, respectively). The untreated pneumonic form of the disease (in which it is inhaled into the lungs) has a mortality rate close to 100% and can kill within 24 hours.

Let’s pretend that you are one of those unlucky people who catches bubonic plague. Most likely, you were bitten by an infected flea, and the nasty bacterium which causes plague (Yersinia pestis) is now swimming around inside your body. What’s going to happen?

Just like a spy entering enemy territory, one of the first things Y. pestis does is go under cover. One of the molecules in its outer membrane, called lipopolysaccharide*, is a dead giveaway to your immune system. So, the bacterium cleverly modifies the structure of this molecule so it no longer alerts the immune system. And how does it know when to do this? Y. pestis can detect the temperature outside. When it is around 37 degrees Celsius (98.6 degrees F.), the bacterium figures it must be inside a warm-blooded mammal.

The bacterium then makes a beeline for your lymph nodes, immune system outposts that are constantly searching for microbial intruders. Because it packs some serious heat, Y. pestis doesn’t mind living there. During its journey, if the bacterium encounters any pesky immune cells, such as macrophages, it jams what looks like a hypodermic needle (called a “type III secretion system“) into the cell and injects several toxins. The macrophage whimpers away with both its pride and ability to defend the body severely damaged.

Additionally, at some point, Y. pestis needs some iron. Your body has quite a bit of that, but it’s wrapped up in hemoglobin and other proteins. One of these proteins, called transferrin, becomes the victim of a highway robbery. Y. pestis releases a molecule called yersiniabactin which has a high affinity for iron. In fact, it loves iron so much, that it is able to physically rip it away from transferrin, and then it brings the iron back to Y. pestis.

Once safely inside the lymph node, Y. pestis replicates. Eventually, your immune system picks up on the fact that something is terribly wrong. The lymph nodes swell up, creating the nasty-looking “buboes” that are characteristic of bubonic plague. The bacteria then migrate through the blood to your lungs, at which point you’re basically cooked.

But, how exactly do you die? Strangely enough, your body kills itself. The presence of so many bacteria in the bloodstream causes your immune system to freak out, triggering a condition called septic shock. Your body’s blood vessels begin leaking, decreasing blood volume. This leads to abnormal clotting and multiple organ failure.

*Lipopolysaccharide was the subject of my PhD dissertation, though not the one from Yersinia pestis. I studied a much less harmful bacterium called Bacteroides.

Source: Salyers AA and Whitt DD (2002). Bacterial Pathogenesis: A Molecular Approach (2nd ed). Washington, DC: ASM Press.