Turning pathogens against each other to prevent drug resistance

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.

See: Penn State University for further details.

Posted by Dr. Tim Sandle