Thursday, October 4, 2012

Microbiome Part 3: Antibiotic Resistance

 Note: This program first aired September 22, 2012.

The germ theory of disease, that certain diseases are caused by microscopic organisms, is well established in traditional western medicine today. Thinkers and healers flirted with the idea for centuries, but it took until the 1800’s in Europe for the idea to gain any traction, and after much controversy and resistance,  and to actually change behavior in many hospitals. Behavior like washing your hands after you finish an autopsy, before you go on to examine your next patient (who might be a woman about to give birth). We’ve come so far with the idea that now seconds after a doctor touches you, they rush to the sink to wash their hands, not wanting to risk their own safety with any of the germs (ie bacteria) that might be on your skin.

By the start of the early 20th century, many scientists and researchers had noticed that certain molds inhibited bacterial growth. This observation and the subsequent experimentation it spurred on led to the development of penicillin and the vast array of modern antibiotics we now have available, ushering in the age of modern medicine and the end of many now easily cured diseases. If you have been paying attention in the last decade or so, you will have heard about the growing problem of some of these wonderfully useful drugs not working anymore. Many of the harmful bacteria that are targeted by these drugs are becoming increasingly resistant to their effects.

Antibiotic resistance is a multifaceted problem. The first is a problem of evolution. Quite simply, there is genetic variation for any given trait in any given population. The variation arises from random mutation, and the ones that end up being helpful to an individual’s survival and reproduction get passed on. Ones that have a negative effect don’t get passed on as much, or at all. That’s evolution in a nutshell: differential reproduction. So in a population of bacteria, there may be a version of a gene that gives that particular bacterium resistance to an antibiotic (more on this in a moment). When we douse the bacteria with something that will kill them, the only ones that live and survive and reproduce are the ones who have that have the resistance gene. So, on an evolutionary level, antibiotics select for resistance genes.

Now let me tell you a story about a cave in New Mexico. It is one of the deepest and most isolated caves in the world. Virtually no one has been down there. Yet, when researchers took samples of bacteria, they found that nearly every strain of bacteria was resistant to at least one type of antibiotic currently in use. As a whole, the cave bacteria were resistant to nearly every antibiotic currently in use. The reason for this is fascinating. Essentially, antibiotics are weapons, and though we discovered them, we didn’t invent them, bacteria did. Bacteria evolved antibiotics to kill other bacteria, and gain competitive advantage in their environments. If humans were to use a chemical weapon, they have to protect themselves with a gas mask. The antibiotic resistance genes are the “gas mask” of a bacteria—the genes protect the bacteria from its own chemical weapon, so it can use it on other types of bacteria. The bacteria in the New Mexican cave demonstrate this—they don’t have antibiotic resistance genes because of us, they have them because of each other.

So the genes for resistance to pretty much all antibiotics occur naturally in normal populations of bacteria.  We know how mechanisms of evolution then select for these resistant genes when we apply antibiotics to a population of bacteria. And we know from our discussion of lateral gene transfer, how readily bacteria will swap genes between species.  Putting these three things together leads to the perfect storm of rampant antibiotic resistance we see in our hospitals today.

The hard part is that we can’t do anything about the first factor (the naturally occurring resistance genes) or the last factor (lateral gene transfer is a process that is 3.5 billion years old and going strong).The only one we have any control over is the evolutionary one, and the only way we have influence there is to refrain from participating, in other words, not using the antibiotics, or at least, not using them unless we really really need them.

So bacteria may be at times our foes. In coming weeks, we will look at the other side of the coin, and examine how they are our friends as well. In fact they are such good friends to us,  that we couldn’t live without them.


References: 

From “Contagion” The Harvard University Open Collection on Diseases and Epidemics: http://ocp.hul.harvard.edu/contagion/germtheory.html

Dr. Hani (2010). History of Antibiotics. Retrieved 19 Sep. 2012 from Experiment Resources: http://www.experiment-resources.com/history-of-antibiotics.html

Science Daily “Key to New Antibiotics Could Be Deep Within Isolated Cave”  http://www.sciencedaily.com/releases/2012/04/120411205423.htm

Genereux, Diane P. and Carl T. Bergstrom “Evolution in Action: Understanding Antibiotic Resistance” Chapter 13 Evolutionary Science and Society