Wool, Soil, and Mail...Er, What Do They Have In Common?

Something funny happened to me last week that I found as inspiration for my first pathogen article. I forgot completely that four years ago at the end of my senior year of high school, I wrote a letter to myself to be delivered four years later. I received the letter and read it and laughed at how naive I was at that age. What was more surprising was that I received another letter in handwriting that was not my own. I opened it in curiosity and there was simply one word haphazardly written in the middle of a piece of torn out notebook paper. It read "Anthrax." Of course, based on the friends I hung out with, I assumed it was both referring not only to my aberrantly high affection towards bacteria even at that age but the 80's metal band of the same name. When I read this I smiled and gave a laugh. I don't think whichever of my friends sent me that letter in high school had any idea that in four years I would be so amused upon receiving it. It was my final graduation gift, a happy farewell from four years ago and another happy farewell to my undergraduate career four years later. 

This got me thinking about everything I had learned about bacillus anthracis, the causative agent of anthrax. Of course, anthrax gained national attention during 2001 when several letters filled with b. anthracis spores were sent to several high profile people including Tom Brokaw. But the history of bacillus anthracis (that's pronounced anth-ray-cis) goes back far before these incidences. Robert Koch, the father of bacteriology, used b. anthracis in 1877 to show that bacteria cause diseases. This was the first time that the bacterial basis for disease had ever been proven beyond a doubt and it became the fundamentals of Koch's Postulates which are still used today as a means of determining if a pathogen is the causative agent of a disease. Basically, he's the man AND he has a pretty sweet beard.

Interestingly anthrax was primarily a disease in people who sorted wool. Animals would become infected with the bacteria after picking it up from the soil where it normally resides in the environment. Humans would become infected as a result of close contact with the infected animal. The disease became known as Woolsorter's Disease and it proved to be rather fatal. 

There are three forms of the disease which depend on where contact with the bacteria is made. This includes cutaneous anthrax (located on the skin as black, necrotic lesions...gross), gastrointesinal (in the stomach after ingesting spores), and pulmonary (inhalation, this is the worst as you will soon see...). Immediately what is interesting here is that the virulence of the disease depends on location of the infection. Cutaneous and gastrointestinal forms are far less severe as a pulmonary infection which suggest that the bacteria has developed mechanisms specifically designed for lung infections and this is exactly the case.

Infections in humans can only be accomplished through the spores. This is a unique adaptation to some bacteria that essentially causes the bacteria to "hibernate" when environmental stresses are high. These spores are incredibly resistant to heat, UV, and antibiotics. Pretty wicked, huh? Anyway, when these spores are inhaled they obviously enter the lungs where they are taken up by macrophages in the lungs. This is where the story gets interesting. A mechanism designed to eliminate invaders is used by the bacteria. The spores are not destroyed within these macrophages and the macrophages unknowingly harbor a dangerous enemy within. The macrophage does what it does, which includes traveling to a lymph node bringing the bacteria with it. At some point the spore reenters the bacillus form and replicates VERY rapidly. The bacillus form is VERY replicative unlike the spore. My professor once said that it could grow in spit! The bacteria secrete a toxin which kills the cell and the bacteria emerge from the macrophage within the lymph node. From here they have a one way ticket into the bloodstream. Thanks to a poly-D-glutamic acid capsule (isn't that catchy?) that surrounds the bacteria they can not be taken up my any other macrophages in the blood. As you can imagine, this is not good for the host which leads to an overload of bacteria in the bloodstream, a condition called bacteremia. This leads to...you guessed it...another kind one way ticket...

So this brings up an interesting evolutionary adaptation that many bacteria employ. They use the defense systems of the host in order to establish a successful infection. This is pretty clever. They wait until the body's innate defenses do what they do and then emerge before the body knows what hit it. Not only this, but there is some unknown temporal trigger that tells b. anthracis to emerge and replicate at the right time. This employs a virulence factor known as the Lethal Toxin, which kills the macrophage, but it's only released when it is most advantageous for the bacteria! This won't be the first bacteria to use this kind of pathway. Evolution has selected for these types of organisms to develop ways of directly invading immune cells, essentially eliminating the struggle of the pathogen to survive the innate immune system...the picture speaks for itself!

Luckily, the government is working hard to develop vaccines and new antibiotics against the bacteria. The University of Illinois at Chicago recently received a government grant of  $14 million to help develop novel drugs to use against the bacteria. Obviously, the problem is getting it to either kill the spore or kill the bacillus itself, both very difficult due to the traits of the bacteria. In my opinion a vaccine against the poly-D-glutamic acid capsule may be useful, but it's definitely a tricky disease to try to combat given the interesting way it causes disease. However, we should all sleep easy because it's super unlikely that any of us will ever become infected with b. anthracis. Isn't biology fun!?