Mutational pathway determines whether drug gradients accelerate evolution of drug-resistant cells
arXiv:1202.5431 · doi:10.1103/PhysRevLett.109.088101
Abstract
Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anti-cancer drugs. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via a mutational pathway involving multiple mutations. We show that a non-uniform drug distribution has the potential to accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but if the pathway is short or crosses a fitness valley, the evolution of resistance may actually be slowed down by drug gradients. These predictions can be verified experimentally, and may help to improve strategies for combatting the emergence of resistance.
6 pages, 3 figures, final version before acceptance to Phys. Rev. Letters. P.G and B.W contributed equally to this work
References in corpus (3)
Cited by in corpus (23)
- Spatial model predicts dispersal and cell turnover cause reduced intra-tumor heterogeneity
- Bacterial growth: a statistical physicist's guide
- Spatial heterogeneity in drug concentrations can facilitate the emergence of resistance to cancer therapy
- TrAp: a Tree Approach for Fingerprinting Subclonal Tumor Composition
- Resist or perish: fate of a microbial population subjected to a periodic presence of antimicrobial
- Quantifying the role of population subdivision in evolution on rugged fitness landscapes
- Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics
- Adapt or perish: Evolutionary rescue in a gradually deteriorating environment
- Hydrodynamic flow and concentration gradients in the gut enhance neutral bacterial diversity
- Antibiotic resistance: a physicist's view
- Range Expansion of Heterogeneous Populations
- Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients
- Quantifying the impact of a periodic presence of antimicrobial on resistance evolution in a homogeneous microbial population of fixed size
- Competing evolutionary paths in growing populations with applications to multidrug resistance
- Exploiting ecology in drug pulse sequences in favour of population reduction
- Mutant fate in spatially structured populations on graphs: connecting models to experiments
- The Moran process on 2-chromatic graphs
- Toward understanding of the role of reversibility of phenotypic switching in the evolution of resistance to therapy
- Short-Range Migration Can Alter Evolutionary Dynamics in Solid Tumors
- The role of mechanical forces in the planar-to-bulk transition in growing Escherichia coli microcolonies
- Minimal models of invasion and clonal selection in cancer
- Evolutionary adaptation is facilitated by the presence of lethal genotypes
- Tackling drug resistant infection outbreaks of global pandemic Escherichia coli ST131 using evolutionary and epidemiological genomics