Scientist at Harvard Medical School have embarked on a quest to provide a large-scale glimpse into the maneuvers of bacteria as the encounter increasingly higher doses of antibiotics and adapt to survive them. For the first time ever, teams of scientist constructed a 2 by 4 foot petri dish and filled it with 14 liters of agar. The goal was to observe how the bacterium Escherichia Coli adapted to increasingly higher doses of antibiotics.
The devices called the Microbial Evolution, and Growth Arena (MEGA) represents a simple mirror into how bacteria adapt and thrive in real world environments. Some of the insights yielded from MEGA include the behavior of the bacteria as it is exposed to increasing doses of antibiotics. Surprisingly, scientist found out that
- Bacteria spread until they reached a concentration (antibiotic dose) in which they could no longer grow.
- At each concentration level, a small group of bacteria adapted and survived. Resistance occurred through the successive accumulation of genetic changes. As drug-resistant mutants arose, their descendants migrated to areas of higher antibiotic concentration. Multiple lineages of mutants competed for the same space. The winning strains progressed to the area with the higher drug dose, until they reached a drug concentration at which they could not survive.
- Progressing sequentially through increasingly higher doses of antibiotic, low-resistance mutants gave rise to moderately resistant mutants, eventually spawning highly resistant strains able to fend off the highest doses of antibiotic.
- Ultimately, in a dramatic demonstration of acquired drug resistance, bacteria spread to the highest drug concentration. In the span of 10 days, bacteria produced mutant strains capable of surviving a dose of the antibiotic trimethoprim 1,000 times higher than the one that killed their progenitors. When researchers used another antibiotic — ciprofloxacin — bacteria developed 100,000-fold resistance to the initial dose.
- Initial mutations led to slower growth — a finding that suggests bacteria adapting to the antibiotic aren’t able to grow at optimal speed while developing mutations. Once fully resistant, such bacteria regained normal growth rates.
- The fittest, most resistant mutants were not always the fastest. They sometimes stayed behind weaker strains that braved the frontlines of higher antibiotic doses.
- The classic assumption has been that mutants that survive the highest concentration are the most resistant, but the team’s observations suggest otherwise.
Click here learn more about this topic and watch a video highlighting the evolution of bacteria on a MEGA plate.