Resource limitation prevents the emergence of drug resistance by intensifying within-host competition

Nina Wale, Derek Gordon Sim, Matthew J. Jones, Rahel Salathe, Troy Day, Andrew Fraser Read

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Slowing the evolution of antimicrobial resistance is essential if we are to continue to successfully treat infectious diseases. Whether a drug-resistant mutant grows to high densities, and so sickens the patient and spreads to new hosts, is determined by the competitive interactions it has with drug-susceptible pathogens within the host. Competitive interactions thus represent a good target for resistance management strategies. Using an in vivo model of malaria infection, we show that limiting a resource that is disproportionately required by resistant parasites retards the evolution of drug resistance by intensifying competitive interactions between susceptible and resistant parasites. Resource limitation prevented resistance emergence regardless of whether resistant mutants arose de novo or were experimentally added before drug treatment. Our work provides proof of principle that chemotherapy paired with an "ecological" intervention can slow the evolution of resistance to antimicrobial drugs, even when resistant pathogens are present at high frequencies. It also suggests that a broad range of previously untapped compounds could be used for treating infectious diseases.

Original languageEnglish (US)
Pages (from-to)13774-13779
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number52
DOIs
StatePublished - Dec 26 2017

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Drug Resistance
Communicable Diseases
Parasites
Pharmaceutical Preparations
Microbial Drug Resistance
Malaria
Drug Therapy
Infection
Therapeutics

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "Slowing the evolution of antimicrobial resistance is essential if we are to continue to successfully treat infectious diseases. Whether a drug-resistant mutant grows to high densities, and so sickens the patient and spreads to new hosts, is determined by the competitive interactions it has with drug-susceptible pathogens within the host. Competitive interactions thus represent a good target for resistance management strategies. Using an in vivo model of malaria infection, we show that limiting a resource that is disproportionately required by resistant parasites retards the evolution of drug resistance by intensifying competitive interactions between susceptible and resistant parasites. Resource limitation prevented resistance emergence regardless of whether resistant mutants arose de novo or were experimentally added before drug treatment. Our work provides proof of principle that chemotherapy paired with an {"}ecological{"} intervention can slow the evolution of resistance to antimicrobial drugs, even when resistant pathogens are present at high frequencies. It also suggests that a broad range of previously untapped compounds could be used for treating infectious diseases.",
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AU - Read, Andrew Fraser

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