Researchers at Harvard Medical School and the Technion-Israel Institute of Technology have designed a model to show the development of antibiotic resistant bacteria. In doing so, the model also demonstrates Darwinian evolution in action. Both antibiotic resistance and evolution are concepts that drastically affect the world around us, but are normally invisible. In some cases, this has left segments of the public with some doubt as to the existence of these phenomena. Widespread acceptance of a concept such as antibiotic resistance can be the first step towards taking action, so it is important to incontrovertibly demonstrate the process.
To this end, the research team constructed a giant petri dish, which they call the Microbial Evolution and Growth Arena or MEGA plate. They filled the plate with agar, a nourishing jelly used in lab settings to feed growing organisms. The next step was to find the right bacteria to work with. Dr. Michael Baym, postdoctoral fellow in microbial evolution at Harvard Medical School, and an author of the study, explains “In order to grow bacteria on a petri dish of that size, it needs to be able to swim, which is something E. coli can do but many other model organisms cannot.”
Using the E. coli bacteria, the researchers divided the plate into segments, and added increasingly higher doses of the antibiotic trimethoprim, chosen because it is well known and well understood among scientists.
The outermost area of the plate contained none of the antibiotic, with increasing doses in sections toward the center section of the plate, which contained 1,000 times the initial dose used in the second outermost section. The researchers used a ceiling mounted camera to take snapshots of the process in the MEGA plate, and then spliced the shots into a time-lapsed video. At each stage, the antibiotic killed off a portion of the bacteria while a smaller portion survived to move on to face a higher dosage of the antibiotic. Each time, the new generations of bacteria evolved to resist a higher and higher dosage of antibiotics, until the bacteria spawned a generation resistant to 1,000 times the dose of trimethoprim that killed their ancestors.
Bacteria contain plasmids, which are small rings of extra DNA that have been understood to increase the spread of antibiotic resistance. In the MEGA plate experiment, bacteria were observed to trade plasmids essential for withstanding the doses of antibiotics.
The researchers found that the development of resistance not only had to with the survival of the “fittest individuals” as Darwinian theory predicts, but also which bacteria were closest to the “frontlines” of advancing to the higher doses of antibiotics.
The researcher’s objectives went further than simply modeling these phenomena. The researchers also, according to Professor Roy Kishony of Harvard Medical School and the Technion-Israel Institute of Technology, sought to “identify evolutionary tradeoffs whereby becoming resistant to one drug confers a cost to the bacteria that we might be able to exploit.” In other words, the scientists hope that further MEGA plate studies may reveal resistance associated weaknesses, which could be exploited to treat patients.