Abstract
Are ‘evolution-proof’ therapies possible? The use of antimicrobials without imposing selection for resistance is conjectured (1, 2) to stop the rise of multi‐drug resistance. Here, I present a theory, validated experimentally, suggesting a strategy to manipulate antimicrobial sensitivity and achieve sustained drug efficacy. The model predicts that accessory microbial species act as drug or carbon sink depending on their drug sensitivity, leading to increased drug tolerance or sensitivity in a focal species. Aided by this theory, I doubled the sensitivity of Escherichia coli MC4100 to tetracycline in 24h sensitivity tests. The effect was maintained for 168h following serial passages akin to those used in evolutionary biology to study antibiotic adaptation in MC4100 (3). This theory, and particularly the experimental data, suggest that evolution‐proof strategies do exist. My theory can provides a framework to design synthetic accessory species that maximise drug efficacy while minimising selection on resistance—opening a new venue to treat bacterial infections and, possibly, cancers.
Competing Interest Statement
The authors have declared no competing interest.