Superbugs: How they evolve and minimize the cost of resistance

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Abstract
The increasing frequency with which antimicrobial-resistant microorganisms have emerged in hospitals and communities has alarmed public health officials worldwide. The emergence of resistance results from the evolution of the sometimes elegant resistance mechanisms that create so-called superbugs, which disseminate by clonal spread or exchange resistance traits with other microorganisms. One major contributor to the emergence of resistance is selection intensity, which is determined by the volume of drug consumption by humans and the agriculture industry. De novo or acquired resistance is often initially associated with a cost to fitness of the microorganism. It therefore seems reasonable to assume that reducing the volume of drug use would slow the evolution and reduce the prevalence of resistance. This assumption has led to worldwide attempts to control the inappropriate use of antimicrobials in the hope of controlling the pandemic of antibiotic resistance. However, microorganisms have learned to adapt in order to survive in ever-changing environments. Superbugs have evolved numerous mechanisms that reduce or eliminate the cost of resistance, and such adaptations may minimize the potential benefits of programs aimed at reducing the volume of drug use. It therefore behooves us to look to other disciplines—such as population genetics, ecology, and mathematical biology—to help us tackle this perplexing and important problem.