Wednesday, October 29, 2008

Chlamydia, The oldest organism on earth?















I work next to a chlamydia lab and their main motto is that you should make sure that any chlamydia you get isn't from the lab.  I am serving on 3 dissertation committees for graduate students in that lab and I have learned a lot about chlamydia. One of the coolest aspects of it is that there are a lot of species of chlamydia. There are species specific to humans, to birds, to reptiles, and even to amoeba. The ubiqity of chlamydia suggest that they have been around for a log time. But also, it's nearly impossible to mutate chlamydia and that's probably because they have been associated with their host organisms for as long as the hosts have existed. They are perfectly adapted to their hosts. There are no external genetic elements that are brought in. There are no unused genes. That kind of optimized genome probably won't arise if a microbe invades a host after it already exists (like Mycobacteriam lepraewhich is losing genes).  A genome like that would occur if the pathogen co-evolved right along with it's host species.

About the diagram:
Chlamydia live inside of their host organisms cells most of the time as elementary bodies, which is a state in which they are metabolically active. Chlamydia are released from host cells as reticulate bodies, which are not very metabolically active, but which can infect new cells. In other words, chlamydia don't get out a whole lot, and when they do, they don't do a whole lot.  They don't have many opportunities for external interaction or acquisition of external genetic material, so they haven't become resistant to antibiotics, but chlamydia infections are really hard to completely cure because they hide out inside of host cells where they are protected from antibiotics.  

Diseases:
While Chlamydia trachomatis is sexually transmitted, it can also be transmitted as an eye infection.  Chlamydia pneumoniae is transmitted through the air and most people test positive for antibodies to it.  It may have a role in atherosclerosis and other inflammatory diseases.

Thursday, October 23, 2008

Sex Ed in the 21st century

In the 4th grade I skipped that day because I was sick (ha ha ha). I really was running a fever, but for once in my life, I was happy about that. I thought that being separated from all of the boys, marched into a gym and shown what a tampon was was not only ridiculous, but also embarrassing.
In the 7th grade, it was a Disney cartoon about syphilis and gonorrhea in which cartoon animations of germs wearing combat helmets were plotting attacks against humanity. It was a kind of edgy video because it showed real-life pictures of genital warts, but mainly I was left with the idea that syphilis looked a lot cooler than gonorrhea.
In the 10th grade, we got an Ob/Gyn doctor who I think really was prepared to say a lot, but when he said that someone could get an STD in any warm wet place and asked the class where those places were, the first answer he got was "An armpit?" from one of the jocks. I guess he didn't know that our previous education consisted mainly of a Disney cartoon, but he seemed so shocked that he gave us a very mild version of what he had planned to teach. (His daughter, who was my friend, told me the horror stories he had prepared for us which were truly gross....I pulled one out the other day on my senior level class at the university and they were revolted.)
Despite these efforts, I think I truly received an appropriate level of sex ed as a post doc in the Rollins School of Public Health at Emory University. (Better late than never eh?) The education came in the form of displays about sexual practices and disease transmission in Africa, studies detailing specific sexual behaviors as risk factors for contracting disease, seminars about sexually transmitted disease and epidemiology problems in which we computed transmission rates. All of the women in the lab made a pact that we would never have sex with anyone without a seeing clean results for a full series of tests for every disease that could be transmitted sexually.
In an environment where most everone had a master's degree or more, it was easy to discuss public health risks with frankness and candor. My initial response to those discussions was initially surprise because of their frankness and candor. Political correctness was discarded (though respect was still maintained) in exchange for discussing solutions to health threats. I was surprised to hear the frequency with which homosexuality in males was indicated as a risk factors for contracting sexually transmitted diseases and some infections such as MRSA that are not typically thought of as STDs.
Of course this made sense when I considered that males transmit many diseases more readily than females and that if sexual contacts are male to male, the overall transmission rate will be higher. I think it was a surprise because I had grown up in the days of the AIDS awareness campaign and was told over and over that HIV was not a gay disease. Of course this is correct, heterosexual individuals get HIV too. What the campaign didn't say was that homosexuality is a risk factor for HIV. The campaign also failed to address the fact that AIDS research was funded by money that had previously been used to contain and treat tuberculosis infections, which have since become one of the greatest causes of mortality among those who have AIDS. I worry that the lack of information disseminated during that campaign, while perhaps promoting the civil rights of AIDS patients, may have contributed unduly to the health burden caused by the disease.
What doesn't make sense to me is why this information isn't more publicly distributed now. I have many gay friends who I hope know these things so that they can make every effort to keep themselves healthy. Sometimes I try to talk to them about these things, but it usually doesn't go over too well, at least in the US. In Amsterdam, I stayed at the apartment of some gay friends and we had discussions of the health risks associated with homosexuality, which they brought up and in some instances knew more than I did. In the US though, these discussions usually end up offending people. In an age where gay rights are emphasized in the US, I would think that the right to know about the health risks associated with the gay lifestyle would be one of the most basic, and would be more widely distributed. We have had seat-belt campaigns, obesity campaigns, skin cancer campaigns, and yes, there have been safe-sex campaigns, but the homosexual specific health related issues are usually left out.

Tuesday, October 21, 2008

Shuffling the deck: Integrons and resistance genes



Maybe the reason I like bacteria so much is that they remind me of little machines. They float around and perform a lot of different functions that keep them alive. Within bacteria, there are also some random processes that occur, (like mutation or recombination). Sometimes these processes benefit bacteria, but most of the time they don't. When the processes go badly, the bacteria that experienced them dies, or gets replaced by bacteria that can grow more rapidly, or use resources more efficiently, or survive longer or whatever. This is no big deal to bacteria because they are clonal, and there are about a zillion more just like them except without the deleterious change. However, if the random event is beneficial, then the payoff is huge. The altered bacterium will rapidly take over the population and dominate it's little microbial world.

Integrons are like decks of cards in bacteria except that instead of cards, they are decks of resistance genes. They are all lined up in one cohesive stretch of DNA and they are linked to each other. Integrons are one way that bacteria can become resistant to lots of antibiotics all at once. The problem with integrons (for bacteria) is that mostly bacteria can only play the first card in the deck meaning that they can only efficiently express the first gene in the integron. If the bacteria are exposed to an antibiotic that they have a resistance gene for, but that resistance gene isn't the first one in the integron, it won't do them much good, because they can't express it. However, just like cards in a deck, the bacteria can shuffle the resistance genes in an integron and reorganize the order they are in. This enables them to change which one is first.

Just like shuffling a deck of cards, shuffling the genes in an integron occurs randomly. However, because bacterial clones usually divide pretty rapidly, there are lots of bacteria that have the integron. When they shuffle their resistance genes, odds are that most of them will end up with the wrong resistance gene in the first position. However the odds are that some of them will end up with the right resistance gene in the front of the deck. Those bacteria will take over the population and go on to cause more infections another day. Now of course I hate the infections they cause, but the way they survive is pretty neat.

Tuesday, October 14, 2008

Antibiotics and the food we eat


I can't recall taking any antibiotics since I was in high school. Not that I haven't tried of course. When I was in graduate school, I had a cough, and ear infections for a long time. I also had crummy insurance and so when I went to the doctor, they told me to drink more water and sleep more. It was probably good advice, but I was really sick. I wavered between shooting myself up with lab antibiotics and talking to a pharmacist. I decided to go to the pharmacist and asked what to do. Pharmacists turn out to be really cool. Besides dispensing drugs, they know A LOT, and they are usually happy to share their knowledge. The pharmacist told me to take pseudofed to help drain my ears and I got better. I apparently didn't need antibiotics after all. Since then, I have just steered clear of antibiotics and although I have been really sick a few times since then, it was always viral and I didn't need an antibiotic. So I felt pretty good about myself. You know, since I research antibiotic resistance, it's the least I can do to not contribute to the problem that I am trying to help solve. But then I found out about antibiotics and the food we eat. Horror of horrors! I contribute to the problem after all because I eat food.

Antibiotics are used heavily in the food industry. They are used both for plants and animals. It is probably impossible to eliminate them entirely from agriculture because plants and animals get sick with bacterial infections. Since agricultural organisms are often in close contact with each other, diseases can spread rapidly so it's usually necessary to treat the entire population to get rid of the disease entirely.
However, sometimes antibiotics are used for purposes other than the treatment of diseases. They are used to enhance the growth of animals. This practice is mainly used in pigs but has also been used in chickens. The reason that antibiotics are thought to increase the growth of food animals is that by killing off some of their gut microbial flora, there isn't as much competition for the food between the animals and their microbes. It might also help eliminate pathogens from the animals.
In the 90s, growth enhancing use of antibiotic accounted for about half the use of all antibiotics. More recently than that, we have learned that many antimicrobials don't break down during the sewage treatment process and so they hang around in the environment selecting for antimicrobial resistance bacteria long after they have passed through whatever organism they were used to treat. The antibiotics used in animals are similar to those used in humans. Resistance to animal antimicrobials is related to resistance to human antimicrobials. At this point, pharmaceutical companies aren't making many new antibiotics, so it's important to make the ones we have last.
In Europe and in Korea, the use of growth promoting antibiotics has been banned because those countries have decided to prioritize human use of antibiotics over growth promotion. (Antibiotics can still be used to treat diseases in animals). In the US however, this hasn't happened yet. I would suspect that the reasons it hasn't happened are that the lobby by the agricultural industry is intensely opposed to this, and there is a huge demand for inexpensive pork.

I know which side of the problem I am on (I don't eat much meat anyway, so if the price goes up, I'll survive). If you are also on the side of prioritizing antimicrobials for humans over growth promotion in animals, you can write to your congressman demanding that antibiotics be eliminated as growth promoters in the agricultural industry so that they will remain effective longer in human populations. You can also eat less pork.

Monday, October 6, 2008

Leprosy, a degrading disease


There is symmetry in nature.  It's one of the best reasons for being a biologist....finding hidden aspects of an organism that parallel its outer nature.  Leprosy is a great example of this.  Leprosy causes nerve damage, skin lesions, and mucous membrane damage.  Although it is one of the oldest disease known to man, it is one of the least understood.  No one knows how it is spread, or why it affects people as it does. Despite the fact that it is not very contagious and that most people are genetically not susceptible to it, leprosy tends to degrade societies.  People with leprosy are quarantined into leper colonies in some countries where leprosy is endemic in the populations.  The quarantine is unnecessary at this point because after only a few days of treatment, infected individuals cease to be contagious at all and were never very contagious to begin with.  However, because of the unpleasant consequences associated with leprosy, many people hide that they have it and thus go untreated.  Thus members of society are lost due to isolation either in leper camps, or  from failure to treat their disease.

Leprosy also degrades body function.  Due to nerve and skin damage, leprosy can disable people.  In 1995 the World Health Organization estimated that between 2-3 million people were permanently disabled from leprosy.  Although leprosy is not directly responsible for limb and digit loss, nerve damage makes those infected with leprosy unable to feel pain and subsequent trauma to their limbs and digits can result in their loss.

Leprosy itself is likewise degrading...or at least its genome is.  Due to its close association with humans, many of its metabolic processes are unnecessary.  It can simply acquire what it needs from humans.  So the unnecessary genes are gradually filling up with mutation, becoming non-functional and degrading away.  (That said, those mutations will not make it go away as a disease.)

It is secretly satisfying that while leprosy has had terrible impacts on humans and society, the association it has with humans has impacted it as well, and in a metaphorically similar way.

Thursday, October 2, 2008

MRSA

MRSA has become the dreaded infection of this decade it seems.  Everyone is up in arms over MRSA....washing clothes with MRSA killing detergents, going crazy with antibacterial soaps, and so forth.  The word "superbug" has come into common use with with MRSA, which evokes images of an unstoppable villain.
In some ways, MRSA has become a more serious threat than in the past.  It is becoming hard to cure once it causes infections, and can cause more serious infections more rapidly than in the past.  This is because it is acquiring more resistance genes and more virulence genes.  Therefore, the best answer to MRSA infections is to not get them.
What are the ways we get Staph infections?

1. Through skin abrasions that are not disinfected.  The populations at the greatest risk are athletes, prisoners, and homosexual men, and especially methamphetamine using homosexual men.  These people tend to have life styles where they get lots of abrasions and have lots of skin contact with other people.  However anyone can get a Staph infection through an abrasion or cut.  The best answer to preventing an infection is to disinfect any wounds on your skin.  While this includes a skinned knee or scrape, it also includes mosquito bites you scratch too much, pimples you pop,  blisters that come open, and razor nicks.
You may say "It's only a flesh wound"  and it may be, but those are not to be underestimated.

2. Surgery.  This is a bad way of getting MRSA, because it is already under the skin and you have to use antibiotics to kill it.  There are still antibiotics that work, so there is still hope, but this isn't good.  Before going in for surgery, I would interview the surgeon, discuss with him my concerns about MRSA and ask what precautions he takes.  If he says MRSA isn't a problem in their hospital, don't buy it...it is a problem in every hospital.  Unless you hear a reasonable list of precautions, such as disposable pens, methods of isolating you (or your wound) while you are opened up,  scrubbing you, scrubbing themselves, MRSA screening of health care workers to make sure they aren't carriers, etc.  find another surgeon if you can.  Most responsible healthcare providers do take precautions against spreading MRSA, but there are a few bad ones out there.  If they express serious concern about MRSA, they are probably okay.  If they don't probably it's a good idea to move on.  

So why is MRSA so bad?

It infects and effectively degrades soft tissue.  This can occur in the skin and causes boils (also called carbuncles and as a pointless piece of trivia, two carbuncles that fuse into each other are called a furuncle).  
This can also occur in the organs and causes sepsis which means rotting from the inside out.

At this point, I wish I had a funny story to tell, because whenever I read about sepsis, it makes me want to cry.  Unfortunately, I can't think of any funny stories about people rotting from the inside out.