Researchers
have developed a large culturing device to track the evolution of bacteria as
they mutate in the presence of antibiotics, revealing that, surprisingly, the
fittest mutants were not those most likely to infiltrate higher antibiotic
concentrations. Instead, bacteria "behind" the very fittest on the
growth plate became capable of surviving at highest antibiotic concentrations.
The
results provide important insights into the evolutionary patterns and
mechanisms that drive bacteria's success in overcoming antibiotics, a
phenomenon that threatens human health worldwide. To better understand the
emergence of antibiotic resistance in space and time, Michael Baym and
colleagues developed a device called the microbial evolution growth arena
plate, or MEGA plate -- a large, rectangular petri dish across which different
concentrations of antibiotics can be applied; here, the researchers used
trimethoprim and ciprofloxacin.
Bacteria
were cultured at one location on the plate; as competition for resources
increased, they spread to other regions. Applying varying levels of
antibiotics, the authors were able to map out mutations that allowed increasingly
resistant mutant bacteria to spread. Bacteria were unable to adapt directly
from zero antibiotic to the highest concentrations, for both drugs tested,
revealing that exposure to intermediate concentrations of antibiotics is
essential for the bacteria to evolve resistance.
Mutations
that increased resistance often came at the cost of reduced growth, which was
subsequently restored by additional compensatory mutations, the authors found.
Intriguingly, the spatial location of bacterial species played a role in their
success in developing resistance.
For
example, when the researchers moved the trapped mutants (those behind their
"fit" parents) to the "frontlines" of the culture, they
were able to grow into new regions where the frontline bacteria could not. In
light of this finding, the authors suggest that the fitness of bacterial
populations is not driven by the fittest mutants, but rather by those that are
both sufficiently fit and arise sufficiently close to the advancing front.
As
Luke McNally and Sam Brown explain in a related Perspective, the MEGA plate
device developed here, which provided "an unprecedented visualization of
[bacterial] evolution through time and space," could be used to explore
additional aspects of drug resistance evolution.
For
further details see:
Posted by Dr. Tim Sandle
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Pharmaceutical Microbiology