Thursday, June 30, 2011

Lister-who, Mono-what!?

I recently heard that the Dole food company had packages of pre-made salads that were contaminated with a Gram-positive bacteria called Listeria Monocytogenes. Alright, all together now... List-ear-e-uh Mono-sight-ah-gen-ease. This immediately paved the way for a new blog post. One of my favorite things to do is to entymologically break down these latin words to a nifty new definition. In this case Monocytogenes would be defined as something to the effect of "Produced in Monocytes" which we'll see why later. Interesting tidbit of info. The bacteria has a flagella which it can use to propel itself around but it only works at room temperature at not at the body's temperature.


Anyway this pathogen was originally discovered in the 1920s but somehow they deemed the bacteria of this genus worthy of the named Lister, a British surgeon from the early 1900s that became famous for the advocacy of sterilization of hospitals and clinics including the tools they use. He's pretty awesome in his own right so maybe whoever named this species found it fitting that this awesome bacteria also be named after an equally awesome guy.

It terms of evolutionary adaptiveness l. moncytogenes wins by a landslide in my book. This is primarily a GI pathogen so it gets ingested into your system. Normally the harsh environment of the stomach would kill anything that gets it, but everey once and awhile some bacteria may get through and be introduced into the small intestines. Here the story gets pretty cool. The bacteria has a virulence factor on its cellular surface called Internalin and these proteins caused M cells to take up the bacteria. These M cells in the intestines function to move foriegn material from the intestinal lumen to a collection of monocytes on the other side. This is good because the Monocytes in this region called the Peyer's Patch (The deep purple region on the pic left) initiate all sorts of immune responses that kill anything else that's around.  The bacteria are shuttled to the monocytes in the Peyer's Patches in the small intestines like everything else. And like everything else the bacteria is taken up by the monocytes.


Now the bacteria is sitting in a phagolysosome which is targeted for destruction. Here's where the bacteria turns nasty. The bacteria secretes another virulence factor called Listeriolysin O. LLO (AHAHA...wait that's not LOL >_< ) creates very large holes in the phagolysosome by physically implanting itself within the membrane. When I say these pores are large I mean it. They're are so big that the entire bacteria can actually fit through! So now l. monocytogenes has a free pass into the cytoplasm of the cell. It prevented it's own death and now has access to the cell from the inside. This is a true cellular invasion is I ever saw one.

Now, listeria produces yet another virulence factor called ActA. This protein acts as a "seed" for host actin polymerization. Wait what creates a what for what??? Ok sorry, I get super excited! Every human cell has a small protein called actin that gathers together and forms long chains. These actin chains, or filaments, act as structural support for cell structure and have roles in mediating cell division, so they're pretty important. So ActA looks kind of like actin and as a result actin starts to form these chains from ActA. The bacteria strategically places the ActA at the end of its body and the polmerization of the actin propels the bacteria forward! So it utilizes the host cells own actin in order to "drive" around via what scientists call the "comet tail." The listeria will eventually push itself against the host cell membrane, and if this happens it can potentially reach into a neighboring cell! So cool! The pic on the right shows the bacteria in orange within the cell cruising along inside using the actin tails which are florescent in green. The green is the tagged actin as as you can see it's all along the border of the host cell which helps the cell hold its shape. If you look near the middle-left of the pic you can even see several bacteria pushing out from the inside of the cell! TOO COOL!

Great, so what? Well what happens is that by using this methods of pathogenesis the bacteria can gain access to whole host of cells (ha that was a pun). It can be transported around the body and can gain access to nerve tissue leading to meningitis or even, as the University of Illinois College of Medicine has shown, invade heart tissue leading to acute endocarditis. It can also arise in the bloodstream and produces severe septicemia leading to shock. Worse yet, this is one of the few pathogens that can actively invade and breach the placental barrier. Sadly 22% of listeria infections in pregnant women lead to the death of the fetus. The wide variety of sever diseases that the bacterial infection can cause make it one of the most dangerous pathogens around. In fact, although infections of l. monocyotgenes is rare it leads to death in a quarter of cases!

Evolutionary this bacteria has taken advantage of several things in order to survive. The first, and by now what I hope is seen as a recurring theme in my posts, is that it directly invades immune cells breaching a very powerful innate barrier in human hosts. Not only that but it also high-jacks a normal cellular response and uses it for its own ends. In this case, the uptake by M cells and the target for degradation are used for the benefit of the bacteria in order to gain full access to the host cell cytoplasm. Listeria is an incredible and effective pathogen because of how versatile it is. The interesting way it works intracellularly makes it one of my favorite pathogens.

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