Figure 1: Lab shenanigans are serious business.
Collateral Sensitivity: Exposing a bacteria to one drug will make it more sensitive to another drug. (Collateral Sensitivity Illustration)
Drug Cycling: Evolving a bacteria in drug A, then evolving a bacteria in drug B, and then returning the bacteria to drug A. (Drug Cycling Illustration)
MIC: (Minimum inhibitory concentration) The minimum amount of drug to inhibit the growth of the bacteria.
Does collateral sensitivity influence the availability of mutations that confer resistance to a different drug?
Antibiotic resistance is rapidly on the rise. Frequently, news articles alert us to new strains of bacteria that have evolved drug resistance, and remind us that our number of effective drugs keeps dwindling. Drug cycling has been proposed as a means of slowing the evolution of new resistant strains. When combined with collateral sensitivity profiles, this technique may be a bacteria's new arch-nemesis. But can the use of collaterally sensitive drug pairs reduce the available resistant mutations the bacteria can acquire in the future? That's what we are setting out to discover.
The Network and Methods:
We have designed a sensitivity network of three drugs (Gentamicin, Colistin, and Rifampicin) that allows us to explore the affects of collateral sensitivity while maintaining the controls of a collateral resistant and collateral neutral drug pairings (Our Network). The network may be expanded in the future to complete a full circle of drug cycling. Currently, we are evolving single-step mutants to the drug gentamicin and subjecting them to varying concentrations of the other drugs to determine the evolved strains' MICs. This will allow us to compare the mutants' MICs to the ancestor's MICs to see if the sensitivity network holds true. We will then sequence the strains to identify mutations and determine whether these mutations do indeed limit the number of future mutations that confer resistance to another drug.
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