Evolutionary ecology meets the antibiotic crisis: Can we control pathogen adaptation through sequential therapy?

Abstract

The spread of antibiotic resistance is a global challenge that is fueled by evolution and ecological processes. Therefore, the design of new sustainable therapy should take account of these underlying processes-as proposed within the field of evolutionary medicine, yet usually not receiving the necessary attention from national and international health agencies. We here put the spotlight on a currently neglected treatment strategy: sequential therapy. Changes among antibiotics generate fluctuating selection conditions that are in general difficult to counter by any organism. We argue that sequential treatment designs can be specifically optimized by exploiting evolutionary trade-offs, for example collateral sensitivity and/or inducible physiological constraints, such as negative hysteresis, where pre-exposure to one antibiotic induces temporary hyper-sensitivity to another antibiotic. Our commentary provides an overview of sequential treatment strategies and outlines steps towards their further optimization.

Keywords: antagonistic pleiotropy; collateral sensitivity; fluctuating selection; negative hysteresis; sequential therapy.

Figure 1.

Strategies for multidrug treatments. Multidrug treatments can be designed in different ways, depending on the temporal structure and the application level. Colours represent different drugs