How Bugs Fight Drugs

Although antibiotics have been an enormous boon to human health, providing successful treatments for a variety of bacterial infections that had been killers for millenia, their use creates selection pressure that leads to the evolution of antibiotic-resistant strains of bacteria.  I’ve written here before about the emergence of new strains of resistant organisms; often, these are first discovered in a clinical setting, when they make someone sick.

The Technology Review has a recent article describing a new approach to understanding the evolution of antibiotic resistance.   Developed by Professor Robert Austin and his research group at Princeton University, the method uses a specially constructed microfludics chip to provide a range of nano-scale environments for bacteria.   The chip contains more than 1,000 tiny hexagonal chambers, interconnected by tiny slits.  A nutrient solution is allowed to flow along one side of the chip, and a solution of the antibiotic ciprofloxacin along the other.  This produces a range of environments in the chip’s chambers, with gradients of nutrients and antibiotic.   This allowed the researchers to observe how the evolution of resistance took place as a function of the local environment.

One of their observations was that developing resistance did not require a great deal of time, even considering the short duration of bacterial generations.

Austin and colleagues began to see resistant strains emerge within five hours. After 10 hours, the resistant strains  were populating even the most Cipro-saturated chambers

What is perhaps more interesting is that, when the experiments were repeated, the same pattern of mutations and evolving resistance was observed.

The researchers also discovered that the evolution occurred predictably. Every time they ran the experiment, they got the same result, with the same four resistance-conferring mutations emerging over and over again.

If this result holds true, it could be of great value in drug development; potentially, drugs could be designed to block the emergence of resistance.  The same technique could also be used to study the evolution of beneficial bacteria, and Prof. Austin hopes that it may also be useful in understanding how some types of cancer cells become resistant to chemotherapy agents.

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