Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa
Abstract
Evolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments with Pseudomonas aeruginosa, and identified three main outcomes: (i) bacteria commonly failed to counter hypersensitivity and went extinct; (ii) hypersensitivity sometimes converted into multidrug resistance; and (iii) resistance gains frequently caused re-sensitization to the previous drug, thereby maintaining the trade-off. Drug order affected the evolutionary outcome, most likely due to variation in the effect size of collateral sensitivity, epistasis among adaptive mutations, and fitness costs. Our finding of robust genetic trade-offs and drug-order effects can guide design of evolution-informed antibiotic therapy.
Data availability
Sequencing data have been deposited at NCBI under the BioProject number: PRJNA524114.All other data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
-
Evolutionary stability of antibiotic collateral sensitivityNCBI Bioproject, PRJNA524114.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SCHU 1415/12-1)
- Hinrich Schulenburg
Deutsche Forschungsgemeinschaft (EXC 22167-39088401)
- Philip Rosenstiel
- Hinrich Schulenburg
Leibniz-Gemeinschaft (EvoLUNG)
- Camilo Barbosa
- Hinrich Schulenburg
Max-Planck-Gesellschaft (IMPRS Evolutionary Biology)
- Camilo Barbosa
- Roderich Römhild
Max-Planck-Gesellschaft (Fellowship)
- Hinrich Schulenburg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Barbosa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,922
- views
-
- 710
- downloads
-
- 70
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Evolutionary Biology
Although fossil evidence suggests the existence of an early muscular system in the ancient cnidarian jellyfish from the early Cambrian Kuanchuanpu biota (ca. 535 Ma), south China, the mechanisms underlying the feeding and respiration of the early jellyfish are conjectural. Recently, the polyp inside the periderm of olivooids was demonstrated to be a calyx-like structure, most likely bearing short tentacles and bundles of coronal muscles at the edge of the calyx, thus presumably contributing to feeding and respiration. Here, we simulate the contraction and expansion of the microscopic periderm-bearing olivooid Quadrapyrgites via the fluid-structure interaction computational fluid dynamics (CFD) method to investigate their feeding and respiratory activities. The simulations show that the rate of water inhalation by the polyp subumbrella is positively correlated with the rate of contraction and expansion of the coronal muscles, consistent with the previous feeding and respiration hypothesis. The dynamic simulations also show that the frequent inhalation/exhalation of water through the periderm polyp expansion/contraction conducted by the muscular system of Quadrapyrgites most likely represents the ancestral feeding and respiration patterns of Cambrian sedentary medusozoans that predated the rhythmic jet-propelled swimming of the modern jellyfish. Most importantly for these Cambrian microscopic sedentary medusozoans, the increase of body size and stronger capacity of muscle contraction may have been indispensable in the stepwise evolution of active feeding and subsequent swimming in a higher flow (or higher Reynolds number) environment.
-
- Evolutionary Biology
What is the genetic architecture of local adaptation and what is the geographic scale over which it operates? We investigated patterns of local and convergent adaptation in five sympatric population pairs of traditionally cultivated maize and its wild relative teosinte (Zea mays subsp. parviglumis). We found that signatures of local adaptation based on the inference of adaptive fixations and selective sweeps are frequently exclusive to individual populations, more so in teosinte compared to maize. However, for both maize and teosinte, selective sweeps are also frequently shared by several populations, and often between subspecies. We were further able to infer that selective sweeps were shared among populations most often via migration, though sharing via standing variation was also common. Our analyses suggest that teosinte has been a continued source of beneficial alleles for maize, even after domestication, and that maize populations have facilitated adaptation in teosinte by moving beneficial alleles across the landscape. Taken together, our results suggest local adaptation in maize and teosinte has an intermediate geographic scale, one that is larger than individual populations but smaller than the species range.