Limiting
a much-needed resource could pit pathogens against one another and prevent the
emergence of drug resistance. New research demonstrates that harnessing
competition among pathogens inside a patient could extend the life of existing
drugs where resistance is already present and prevent resistance to new drugs
from emerging.
Drug
resistance originates when a pathogen -- such as a parasite, virus, or
bacterium -- develops a genetic mutation that allows it to avoid being killed
by the drug. Even if only one individual pathogen has this mutation, as is
frequently the case when resistance first arises, that one individual can
replicate into a population of billions once it survives drug treatment. But
resistance often comes with a cost, and drug-resistant pathogens often do not
acquire certain resources as efficiently as other pathogens, or they may
require more of the resource.
The
researchers manipulated a nutrient in the drinking water of mice that is used
by malaria parasites during an infection -- just as a gardener might manipulate
nutrients through fertilizers to favor certain plants. This dietary
intervention was used alongside traditional drugs as a sort of combination
therapy.
The
researchers then confirmed that their results were due to competition among
parasites and not some other effect of limiting the nutrient. When drug-treated
mice were infected only with resistant strains and the nutrient was limited,
the resistant parasites survived. But when drug-treated mice were infected with
both sensitive and resistant parasites, limiting the nutrient stopped resistant
parasites from growing at all -- even when resistant parasites were initially
present at far greater numbers than when they typically first appear in a host.
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