Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Competition delays multi-drug resistance evolution during combination therapy

View ORCID ProfileErnesto Berríos-Caro, View ORCID ProfileDanna R. Gifford, View ORCID ProfileTobias Galla
doi: https://doi.org/10.1101/2020.05.27.119537
Ernesto Berríos-Caro
aTheoretical Physics, Department of Physics and Astronomy, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester M13 9PL, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ernesto Berríos-Caro
  • For correspondence: ernesto.berrios@postgrad.manchester.ac.uk
Danna R. Gifford
bDivision of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Danna R. Gifford
Tobias Galla
aTheoretical Physics, Department of Physics and Astronomy, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester M13 9PL, United Kingdom
cInstituto de Física Interdisciplinar y Sistemas Complejos, IFISC (CSIC-UIB), Campus Universitat Illes Balears, E-07122 Palma de Mallorca, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tobias Galla
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Combination therapies have shown remarkable success in preventing the evolution of resistance to multiple drugs, including HIV, tuberculosis, and cancer. Nevertheless, the rise in drug resistance still remains an important challenge. The capability to accurately predict the emergence of resistance, either to one or multiple drugs, may help to improve treatment options. Existing theoretical approaches often focus on exponential growth laws, which may not be realistic when scarce resources and competition limit growth. In this work, we study the emergence of single and double drug resistance in a model of combination therapy of two drugs. The model describes a sensitive strain, two types of single-resistant strains, and a double-resistant strain. We compare the probability that resistance emerges for three growth laws: exponential growth, logistic growth without competition between strains, and logistic growth with competition between strains. Using mathematical estimates and numerical simulations, we show that between-strain competition only affects the emergence of single resistance when resources are scarce. In contrast, the probability of double resistance is affected by between-strain competition over a wider space of resource availability. This indicates that competition between different resistant strains may be pertinent to identifying strategies for suppressing drug resistance, and that exponential models may overestimate the emergence of resistance to multiple drugs. A by-product of our work is an efficient strategy to evaluate probabilities of single and double resistance in models with multiple sequential mutations. This may be useful for a range of other problems in which the probability of resistance is of interest.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted May 30, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Competition delays multi-drug resistance evolution during combination therapy
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Competition delays multi-drug resistance evolution during combination therapy
Ernesto Berríos-Caro, Danna R. Gifford, Tobias Galla
bioRxiv 2020.05.27.119537; doi: https://doi.org/10.1101/2020.05.27.119537
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Competition delays multi-drug resistance evolution during combination therapy
Ernesto Berríos-Caro, Danna R. Gifford, Tobias Galla
bioRxiv 2020.05.27.119537; doi: https://doi.org/10.1101/2020.05.27.119537

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Evolutionary Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4866)
  • Biochemistry (10821)
  • Bioengineering (8068)
  • Bioinformatics (27381)
  • Biophysics (14030)
  • Cancer Biology (11165)
  • Cell Biology (16106)
  • Clinical Trials (138)
  • Developmental Biology (8808)
  • Ecology (13332)
  • Epidemiology (2067)
  • Evolutionary Biology (17399)
  • Genetics (11705)
  • Genomics (15963)
  • Immunology (11061)
  • Microbiology (26168)
  • Molecular Biology (10680)
  • Neuroscience (56746)
  • Paleontology (422)
  • Pathology (1737)
  • Pharmacology and Toxicology (3012)
  • Physiology (4569)
  • Plant Biology (9669)
  • Scientific Communication and Education (1617)
  • Synthetic Biology (2699)
  • Systems Biology (6997)
  • Zoology (1515)