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.

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.



   

Don't Drink That Water!!!

I'm sure everyone remembers the powerful earthquake that struck Haiti in 2010. The 7.0 magnitude earthquake ravaged the Haitian landscape leaving cities and people in ruin. Beside the obvious destruction the earthquake produced it also brought about serious health risks. I remember watching the news and seeing these families in tent cities. Anderson Cooper, of course, interviewing the people and giving the world a view of unimaginable poverty (his infamous black shirt is depicted right being given a medal for spreading fear). At the same time I thought, "these people are going to get sick. It may not happen today, or tomorrow, but at some point an outbreak of something will occur." In December 2010 an outbreak of cholera began, marking the beginning of the one of the worst cholera epidemics in modern times.

The story of cholera has its origins way back in history. Like many other illnesses, people in the 19th century knew the disease cholera. In fact it was the first reportable disease in U.S. history. In 1854, the world changed with the use of keen observation. Throughout history, diseases like the plague were thought to have two sources. One was God and the other was the miasma theory. The first being that God punishes humanity by means of disease and the second being that the deadly fumes from swamps and the dead bring about disease. A English physician named John Snow was skeptical to the miasma theory of disease and being the good physician he was decided to investigate the clusters of cholera outbreaks in England.  He used a map and plotted the locations are those infected. Then he placed this map over a map showing the drinking water system throughout London. He saw that every infected area drew its water from a single well. After debate with authorities, Snow finally got them to close the well and like magic the incidence of cholera dropped. It's because of this simple observation that Snow became the father of epidemiology, a path that I would like to follow some day myself.

From the observation that sewage contaminated water was the source of disease, Robert Koch (the man! see the first post. He's the one with the sweet beard!) used his own methods to show that cholera was in fact caused by a bacteria. Just like anthrax, cholera was not transmitted by a miasma but a bacillus that named vibrio cholerae. Together Snow and Koch developed the fundamentals of bacteriology and epidemiology: Infectious diseases are caused by bacteria and each one was a particular route of infection.

If yersinia pestis is the Black Death then vibrio cholerae is surely the White Death. The reason is simple enough, it causes a sever diarrhea that is white. Yes I'll say that again it's white, like rice water, hence the condition called Rice Water stool. It doesn't have a smell nor a color. Essentially it's just water that is leaving the body. If left untreated it will probably kill the host. This is why many cartoons were made in the early 20th century that portray cholera as Death or Death spreading cholera. I love the top of that picture the most, it made me laugh.

The pathogenesis of vibrio cholerae begins with its two plasmids. These plasmids contain two pathogenicity islands (clusters of genes coding for virulence traits) coding for the toxin and an adhesin respectively. Interestingly, the clusters of genes coding for the toxin are now believed to have been derived from a bacteriophage that injected its genes into a harmless virbio. The bacteria is initially ingested and then adheres to the epithelial lining of the intestinal tract. This is why it has the adhesins. The next thing that occurs is the secretion of the cholera toxin.

So, vibrio cholerae secretes the toxin into the environment. This toxin has a ton of individual components but can be broken down into two main parts. The first is the receptor binding domain (B domain), which is a series of five peptide subunits that act together for the toxin to bind to the GM1 ganglioside on the surface of the intestinal epithelial cell. I know, I know...a ganglio-wha? It's essentially a sugar molecule that extends off the host which it uses for signalling with other cells. Anyway, once it binds the GM1 ganglioside the cell takes the toxin up via endocytosis like it would to anything else that gets bound. Inside the vesicle, the receptor binding domain releases from the catalytic domain (A domain), the part of the toxin that ends up doing the damage. The A domain passes through the B domain which releases the A part into the cellular cytoplasm. The picture to the left shows the cholera toxin with the B domain on the bottom and the A domain on the top.

Now the story get's cool. If you read the e. coli post this'll sound familiar. So, the toxic A domain ADP-ribosylates a G protein on the inside surface of the cell membrane. By adding this small molecule the G protein can no longer regulate the enzyme adenylate cyclase by turning it off. The result is that this enzyme stays on, and makes a large amount of the molecule cAMP. This molecule acts on ion channels causing ions within the cell like K+, Ca 2+, and Na+ to leave the cell. Due to osmotic force, water inevitably follows and leaves the cells. The water goes into the intestinal lumen and this is the source of the "rice water stool" seen left. Not pretty...

The result of this drop in water volume leads to hypovolemic shock which leads to kidney failure and death. It's for this reason that physicians use a series of ions including sugar as treatment. Interestingly, the sugar channels are not effected by the toxin, so by bringing sugar into the cell water will follow and flow back into the cell hopefully stopping the watery diarrhea. Super clever! We can use osmolarity against the disease which is ruled by osmolarity! What's important is that they replace the amount of water that is lost. In order to do this clinics use the so called "cholera cot." It's a cot with a hole in it with a bucket that measures the amount of water that is expelled from the body. Very simple but super effective!

Cholera remains as a disease exacerbated by poverty. Indeed cholera is a disease not commonly found in the modern world, but runs rampant through underdeveloped nations where human waste contaminates the drinking water. Luckily, it's an easily treatable disease and if treatment is given promptly and effectively it should be cleared on its own. Antibiotics are usually not prescribed unless it is severe. 

Vibrio cholerae has played a serious role in history effectively shaping how epidemiologist started to understand how bacterial diseases are spread. Importantly, in modern times Horizontal Gene Transfer has resulted in the transfer of the cholera toxin to previously avirulent types of bacteria like e. coli. Likewise, this same process resulted in vibrio's acquisition of the toxic genes in the first place! In the wondrous world of biology we have to appreciate how these bacteria evolve so quickly. We also have to recognize that in order to address the spread of these diseases we need to help nations with simple necessities like clean drinking water. 

So You Have A Virus...Some Antibiotic Should Clear That Right Up

I was watching the news tonight and was taken aback by a very small phrase. As we are all well aware, the Center for Disease Control and Prevention (the CDC, the holy grail of work places for me) has been tracking the course of deadly e. coli that has recently surfaced in the U.S. The news was covering this story when the anchorman said "This virus..." I cringed.  He had implied the e. coli, a bacteria, was a virus. This is the sin amongst all sins in the microbiology world. Thinking about it I realized that many people see the terms "bacteria" and "virus" as interchangeable. More importantly, this habit would lead one to believe that they are the same. This post intends to draw a clear distinction between a bacteria and virus and examine how evolution had played a role in the persistence of each.


I'll begin with the virus. Let's take a trip back to the beginning of life. I'm not talking about primitive amoeba, I'm taking further back than that. The story of the virus may well begin at the beginning of life itself. At some point in time a layer of fat was able to surround a randomly attached molecule of base pairs. Thanks to Carl Woese (UI ftw!) it is now plausible to believe that this molecule was RNA as it is much more primitive than our double stranded DNA, hence what he called the RNA World.We'll skip a few million years until this thing ("life" sounds like a stretch for a fat covered bubble) somehow gained the ability to replicate its own genetic component. This is another piece of evidence for the RNA World because RNA can use itself as a mechanism to replicate its own sequence. Anyway, at some point the RNA in this thing somehow left its original sequence by an unknown cause (if you thought transposon, the jumping gene from a previous post, then you deserve a cookie). More importantly this RNA could no longer be replicated unless it is within its parent. This rouge RNA, by the laws of physics, buds off the thing and the result is a separate fat covered bubble that now has a bit of RNA that can be replicated only when its back inside of the host. This is a very murky description of the creation of the primitive virus. In case you're wondering, "The Thing" in John Carpenter's horror movie replicated and disguised itself much live a virus in nature, hence my word choice.

Protein Capsid of Herpes Simplex Virus-A which
 houses the genome of the virus

Note that for viruses I used the word "persist" and not "survive." "Survive" implies that viruses are a living organisms. This is not the case for several reasons. They do not replicate on their own. That's a biggie. The other big one is that they do not produce their own energy. A lot of scientists disagree and do consider viruses to be alive, but by the biological definition they are in their own grey area of existence.

Viruses can come in many flavors which are based on the genetic material they have. They can be single stranded (ss) RNA, double stranded (ds) DNA, ssDNA, and dsRNA. Interestingly, viruses are the only things on Earth that have dsRNA and your cells have evolved a receptor that specifically bind this molecule. If dsRNA gets bound the cell knows its being attacked by something really foreign and really bad, so it usually kills itself right away to prevent viral replication. Sorry, I get so excited about viruses that I can get sidetracked! They can also have a lipid envelope or they could be "naked" and only have a protein capsid that holds the genome inside.

Evolution has done something pretty crazy with these guys. They pack their genomes full of genes in extraordinary ways. Unlike us, viruses can have multiple coding regions of genetic material that overlap with each other. Basically, by starting the process of translation in a different spot, they can make fully functional proteins. If we tried that we'd end up with junk! For instance take the phrase "The Fat Cat Ate The Rat." All three letter words that make a perfect little message we can all understand. Let's say hypothetically instead of started at the first T you start at the H instead. Try reading it in the same sequence of three letters...of course you can't because it doesn't make any sense. But in the viral world such a message would make perfect sense. Because of this phenomenon, viral genomes are can be very small but pack a ton of different genes. Pretty cool, huh?

Now for bacteria. Unlike viruses, bacteria are alive. They replicate on their own and they produce their own energy through super fun metabolic pathways that become not so fun when you're taking a biochemistry class. Bacteria are far more complex than a virus, with genomes that are much larger and produce many more different kinds of proteins. In order of complexity the progression is virus << bacteria< eukaryote. That being said, bacteria were probably the first complex forms of life on Earth. And as long as they've been around, a virus has been around to infect and replicate inside. So as history progressed and cells became more specialized, the virus also had to adapt in order to be able to infect these new kinds of cells.

This is the bare bones of it. I'll do a much more expansive examination of viruses later because I realized I have a lot to say about them because they are super primitive but can do things that make the heads of scientists explode. The point to all of this is that bacteria and viruses are not the same. So if you have a bacterial infection, antibiotics will hopefully take care of the problem. However if a doctor prescribes antibiotics to you after diagnosing you with a virus, you are wasting your time because you can't kill what isn't alive.

The Plague of Our Generation

My generation has seen a couple of pandemics and pandemic scares. From H5N1 influenza (the dreaded bird flu which never came to fruition) to H1N1 (the swine flu which did spread across the world) and from SARS to anthrax the media has time and again presented the danger that these agents have on world health. But truth be told none of these have had the impact from both a social and medical perspective than has the HIV pandemic. This year marks the 30th anniversary of the first reported instances of HIV in the US and I thought I would take a little time to remind everyone what this virus has done not only to those infected but how it has also been a pandemic with great social implications.

The story of HIV and AIDS begins fifty years ago in Africa. This virus has great similarity to a similar virus called the Simian Immunodeficiency Virus and it is widely agreed that fifty years ago, a virus similar enough to SIV evolved the ability to infect humans. Thus, some poor human in Africa came in contact with simian blood and with it came a new virus that would begin the worst pandemic in human history. Twenty years later on June 5th, 1981 doctors in the US started to note something very strange. In LA there were five patients with a peculiar case of pneumonia caused by a bacteria that wouldn't normally infect a human with a healthy immune system. Immune titers from these patients confirmed that all of those with the pneumonia had a severely compromised immune system, with white blood cell counts as low as 200 per uL, only 14% of what a normal count should be.

As media spread coverage of this strange new virus one thing started to stand out amongst the patients infected: they were gay. Not knowing what this new disease was it gained the name GRID, gay-realted immune deficiency, however later it became clear that the virus didn't only effect the homosexual population and the name was changed again. Still, the gay population became stigmatized for harboring this virus and the true face of HIV emerged. Freddy Mercury, the singer of Queen, literally took the knowledge of his infection to his death bed in 1991. Even today, thanks to the media, HIV infection has become synonymous with homosexuality, drug use, and sexual misconduct the end result of of which is invariably the contraction of HIV.


In the 80's the infection also became a death sentence. With no treatment available for this disease those infected could only wait until they became infected with a normally harmless bacteria and the body was overrun. Because of this, partners would leave each other once HIV was diagnosed seeing it as a mark of imminent demise given from the person they loved. Luckily, miracle drugs emerged that could prolong the life-span of the infected for years and years and HIV. Now, HIV is no longer a death sentence and has turned into something more of a chronic illness.

The human immunodeficiency virus  infects CD 4+ T cells, also called T helper cells. These cells are charged with the responsibility of helping clear foreign agents from the blood. The virus binds to the cell and fuses its membrane with the host cells, causing the virus to release a protein capsid into the cell's cytoplasm. The capsid falls apart and releases the true monster into the cell, it's RNA. The RNA genome is reverse trasncribed by a unique enzyme called reverse transcriptase and becomes DNA. Worse, the DNA is taken to the host genome and another enzyme called integrase inserts the genome into the host cell's. As the cell replicates, it unknowingly produces more virus particle by the constant replication of the host genome which now houses the virus's genome too.


The wonder drugs target reverse trasncriptase prevent the production of DNA, and thus any step that comes after. The identification of this enzyme proved a leap forward in the field of biology. The central dogma has always been DNA--> RNA --> Protein. That's the way life works. It's the schema that makes you you and makes me me. From skin to hair, every organism on Earth is under the influence of this genetic process. This is why when researchers said they found an enzyme that makes RNA into DNA (RNA --> DNA) the scientific community scoffed at it, unable to believe that the central dogma which rules all of biology at the level of the gene could possibly be broken. However, the scientists prevailed and would be rewarded with the Nobel Prize.

This enzyme also proves the be the necessary driving force behind the evolution of the virus. The problem is that reverse transcriptase does not have a proofreading mechanism like the DNA polymerases in your cells. In humans, mutations in DNA are bad so the machines that make DNA have methods of checking their work and fixing mistakes. But, in microbes eliminating this mechanism can proove beneficial. Since the replication rate of microbes is so much more frequent than any other organism, if you eliminate the proof-reading, you can potentially cause mutations that allow the pathogen to produce functional proteins but with slightly altered attributes. This could mean the ability to bind a different receptor or in the case of HIV, the evasion of drugs. This is why new drugs are constantly developed for HIV. Reverse Transcriptase can mutate the genome and prevent it from being recognized by the drugs.

Today in the US, the infection rate of HIV is down thanks to the scientific understanding of the virus and education of students about sexual health. However, we cannot hope to solve the pandemic unless we help those that truly need help. No region needs more than the countries in Sub-Saharan Africa which show higher rates if infection than any other region. It's up to the WHO to develop a plan to deliver the aid and drugs necessary to help. Not only that but we need education in the region too. South Africa employs a HIV positive Sesame Street character named Kami in order to achieve this end. Even here though there is a great divide between the rich and poor. 80% of the citizens in South Africa receive treatment from public clinics which are understaffed and not equipped to help all those in need. In a region that is skeptical about the actions of western culture, we must also be mindful of how we would instigate such an intervention.

Although we have the medical means necessary to fight the disease what it really comes down to is money. Poor people and poor countries cannot afford the drugs, a point satirized in South Park where the cure to HIV is "concentrated cash." Also, drug users that don't have access to clean needles are also at risk of contracting HIV and other blood-bourne pathogens. There needs to be an investment in the research for a vaccine to the virus as well as preventative care not only here in the U.S. but worldwide. It's only with this amount of cooperation that we can ever hope of nearing a day where the infection rate and mortality rate of HIV is 0.

When Bacteria Get It On

I've alluded to this phenomenon in the previous blog post about e. coli (check it out b/c it's awesome, like everything I write). It is known as Horizontal Gene Transfer, or HGT for short. There are four processes that are included in HGT which are conjugation, transduction, transposons and plasmids, and transformation. In the world of pathogens this is the way that new traits are obtained quickly and efficiently between organisms and it is probably the most important principle in the quick evolution of pathogens. This exponentially increases the genetic variation within the species of bacteria and produces bacteria with brand new phenotypes we've never seen before.

Let's start with conjugation. Enter Marvin Gaye because they are about to get it on! Ok so bacterial sex may be a bit of an exaggeration but it's easy to see why the process of conjugation has become perceived in this way. In this process a bacteria that contains the "sex pilus," a series of proteins on the bacteria membrane, extends and makes contact with a neighboring bacteria. The pilus can then contract which draws the bacteria closer together and finally, their membranes make contact. Now, essentially their is a direct link between the bacteria called a conjugation bridge. This allows easy passage of genetic material from the donor cell to the recipient and the recipient cell now contains whatever genes were sent through the conjugation bridge.


Plasmids and transposons are transmittable genetic elements that can be transferred through conjugation and really any other process in HGT. Plasmids are uber important...seriously, plasmids run the show in terms of bacterial evolution. These are small, circular bits of DNA that is now contained within the genome of a bacteria. These plasmids usually have genes that allow bacteria to survive in a different niche. Antibiotic resistance is usually conferred to bacteria via plasmids. More importantly, these plasmids are highly stable and easily transferred through the conjugation bridge. The end result is that both bacteria end up with the plasmid! BOOM!



Transposons are like Rick James...super freaky. These things are small bits of DNA that can actually "jump" out of a genome! Yep that's right, these little guys jump out of one bacteria's genome and can recombine into another's, bringing whatever genes it carries along with it. Again, conjugation allows easy transfer through the conjugation bridge. Transposons are pretty nuts and I don't even know the entire details of how these things work, but they are very important in bacterial evolution. In fact, a ton of the human genome has been found to be derived from transposons!



The next method of Horizontal Gene Transfer is transduction. This is the injection of genetic material into a bacteria via a bacteriophage. Those are those weird alien looking things that you've probably seen somewhere before labeled "virus." Yes, those are viruses but they only infect bacteria which is why when you see them in movies infecting humans, it's wrong! After injecting the genetic material into the cell, it can recombine within the genome of the bacteria and it now has whatever genes it gets from the bacteriophage. The shiga toxin from e.coli is one of many genes controlling toxin production that is believed to have entered the bacteria via this method.

Transformation is the last form of HGT. Here, a bacteria becomes "competent," or able to take up extracellular genetic material. What happens here is that bacteria that have holes in their membranes are able to take up genetic material from outside of the cell and then recombine it into their genome to obtain the traits. The DNA is obtained after cells die and rupture, releasing it's genetic material to surrounding cells. It's important to understand however that not all bacteria are able to do this naturally. Labs take advantage of an electric shock to make cells competent so they can insert whatever plasmids or other DNA they want to insert into bacteria. Some bacteria are naturally competent, like neisseria gonorrhoeae (last time I'm spelling that), and can take up DNA if it's available.


Through these methods, bacteria can obtain a wide variety of genes very quickly. Instead of waiting millions of years for evolution to produce better mechanisms of survival, bacteria can obtain new genes and immediately express new phenotypes without having to wait. This has been a scourge to the medical field due to the increase in antibiotic resistance in bacteria seen in hospitals. What's awesome here is that genes can cross genus and species lines from bacteria to bacteria, an impossible feat for humans. Imagine how awesome it would be to be able to exchange DNA with tigers, wolves, or birds and be able to recombine and express those genes! People could have bird wings, tiger strips, and wolf fur!