The Black Death

...And with those two words we begin the tale of one of the most feared pathogens in the world. We've all heard of the times of the Black Death. How it claimed the lives of an estimated 30-60% of the European population during the 14th century. How it caused the disturbing symptoms of painful necrotic swelling. How it was feared throughout Europe. But behind this story there is another. It's here that we come face to face with the culprit and see why it is so deadly. So let us delve deeper into the world of yersinia pestis better known as The Plague. The cartoon on the right is a bacterium singing "Ring Around the Rosy," a poem written in response to the Plague, one of the many legacies the scourge passed onto the human race.


Yersinia pestis was discovered in 1894 during an outbreak of Plague in Hong Kong. By now, Koch's postulates were regarded as the experimental way scientists found the agents of disease and Alexandre Yersin used them in order to discover that this simple gram-negative (turns pink during a gram stain) rod shaped bacterium was the source of Plague.  Over one-hundred years later modern scientists in 2010 used bodies from England, France, and the Netherlands to experimentally prove one and for all that y. pestis was the bacteria that was the source of the Black Death, a fact that was under serious debate my bacteriologist throughout history

So the commonly held theory is that during the 14th century the reservoir (the organism that harbors the agent without displaying symptoms itself)  of the bacteria, rodents, took a sailing trip to Europe on trading ships from Asia. The blood of these rodents were then taken as a blood-meal for the common flea ingesting the bacteria with it. Due to the unsanitary conditions of the 14th century the fleas were able to leap onto humans. The bacteria coagulates the blood meal within the flea literally starving it. As the flea bit the human for another meal it regurgitated the blood and injected the bacteria into the human host. It's at this point that the Black Death would make history not only for the lethality of the disease it caused but for the changes it would bring to the practice of medicine.

One such change was what would become known to us as quarantine. As knowledge of the Black Death spread across Europe, cities had to take their own measure in order to protect their citizens. One instance was in 1377 in the town of Dubrovnik, Croatia. Here the town decreed that travelers and ships had to be isolated for 40 days in order to see if symptoms would appear. They called this practice "quaranta giorni," meaning "forty days" in the Venetian dialect of Italian. This was then simplified to "quarantine." Needless to say that the practice of quarantine exist as one of the simplest and most effective ways to prevent an infection in health care professionals, friends, and family.

Aren't the similarities between this and the next pic uncanny!?

Another major change came to medicine out of a misinterpreted view of disease. Like so many other diseases doctors during the Black Death era saw the pestilence in the form of a miasma (see the cholera post...it's awesome you won't regret it!). As a result doctors fitted themselves with garments that would prevent the miasma from entering their bodies which would prevent the disease when they were working with patients infected with the plague. What they ended up with was a long overcoat that covered them from head to foot and a beak-like mask that was filled with herbs and flowers. Essentially, this strange looking costume became a biohazard suit! It was an airbourne pathogen, so the mask acted as a respirator similar to what would see today. You can see the similarities right? I like to think that this tradition continued and became not only the first biohazard suits but also the first lab coats! But, I have no proof of this claim, it'd just be cool!


Finally, the Plague began a very dark practice in science. This was the first instance in recorded history that people used disease in warfare. Invading armies would hurl Plague infected corpses over castle walls spreading the disease by force. Obviously this idea persisted and became Biowarfare. Today y. pestis is listed as a class 3 BSL agent (Biohazard Safety Level) meaning that it can cause a severe and lethal infection of humans if inhaled but for which treatment exist. In modern times y. pestis infected fleas were released with wheat and rice by Japan over China in 1940 killing 120. It's clear that because of its history y. pestis is viewed highly by individuals seeking militaristic ends via biological means.

Alright, now that we have a bigger view of yersinia pestis as it pertains to history let's talk biology. The lethality of this bacteria comes from its unique pathogenic cycle in humans. Like I said the accepted cycle is rat --> flea --> human. After the flea injects the bacteria into the human host's bloodstream it immediatly disemminates to a nearby lymph node. Here, the bacteria does something that we will see again and again with severe infections. It invades a macrophage and dampens the inflammatory response.

In order to achieve these ends, yersinia uses one of those fancy syringe-like structures (called a Type III secretion system) to inject the macrophage with a series of proteins called Yops. These Yops all vary in their function but the common theme is that they function in cleaving proteins necessary for the inflammatory response. This is the go-to response for infection. It signals immune cells to proliferate and communicate with other cells that produce antibodies. This is all accomplished by signalling molecules called cytokines. By preventing phagocytosis and the release of cytokines, yersinia essentially has a free ride in both its replication cycles and its entrance into the bloodstream. Of course while in the lymph node it kills the cells which causes the black and swollen lymph nodes from which Bubonic Plague gets its name.

Now that y. pestis is in the bloodstream of the human it will eventually disseminate into the lungs thanks to the circulation of blood. If the overload of bacteria in the blood doesn't kill the host due to shock then the disease becomes Pneumonic Plague (the white blotch seen on the x-ray right) when the bacteria reaches the lungs. It's this stage that really ends up killing the most people. The bacteria can survive in the lungs and when the host coughs they release the bacteria into the air which can be breathed in and infect another person. By becoming airbourne, the bacteria vastly increases the probability that it will infect another host. As you will see in other posts, transmission via aerosols is by far the most advantageous method used by pathogens.


I hope you have seen the similarities between y. perstis and b. anthracis (second post! Read it!). Both pathogens have evolved the unique ability to evade the immune response and disseminate into the blood. What's interesting is that they both use different methods to achieve the same end. Anthrax toxin kills the macrophages in the lungs while Yops kill them in the lymph nodes. Both Anthrax toxin and Yops also inhibit phagocytosis, but again the location is different. Evolution has pushed these organisms to infect a specific location even though they have mechanisms that do the same thing. Different evolutionary stresses have caused these pathogens to infect a different location, but the functions of these protein have been beneficial to the organism in its replication and survival.

Evolution functions to tweak ever so slightly what the bacteria already have. Over time bacteria can develop new ways of infection. Perhaps in the case of yersinia it was once strictly an infection of the flea's GI tract. But somewhere in its evolution it developed the ability to infect humans. This jump probably didn't happen overnight. It may well have just been a simple mutation that went overlooked for thousands of years until it finally came in contact with the human host. Many pathogens can change for its benefit and the end result is a pathogen that is all the more frightening.