English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Since penicillin was discovered about 90 years ago, we have become used tousing drugs to eradicate unwanted pathogenic cells. However, using drugs tokill bacteria, viruses or cancer cells has the serious side effect of selectingfor mutant types that survive the drug attack. A key question therefore is howone could eradicate as many cells as possible for a given acceptable risk ofdrug resistance evolution. We address this general question in a model of drugresistance evolution in spatial drug gradients, which recent experiments andtheories have suggested as key drivers of drug resistance. Importantly, ourmodel takes into account the influence of convection, resulting for instancefrom blood flow. Using stochastic simulations, we study the fates of individualresistance mutations and quantify the trade-off between the killing ofwild-type cells and the rise of resistance mutations: shallow gradients andconvection into the antibiotic region promote wild-type death, at the cost ofincreasing the establishment probability of resistance mutations. We canexplain these observed trends by modeling the adaptation process as a branchingrandom walk. Our analysis reveals that the trade-off between death andadaptation depends on the relative length scales of the spatial drug gradientand random dispersal, and the strength of convection. Our results show thatconvection can have a momentous effect on the rate of establishment of newmutations, and may heavily impact the efficiency of antibiotic treatment.

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients