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    Spatial structure facilitates the accumulation and persistence of antibiotic-resistant mutants in biofilms

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    Author
    France, M.T.
    Cornea, A.
    Kehlet-Delgado, H.
    Date
    2019
    Journal
    Evolutionary Applications
    Publisher
    Wiley-Blackwell
    Type
    article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1111/eva.12728
    Abstract
    The emergence and spread of antibiotic resistance in bacterial pathogens are a global crisis. Because many bacterial infections are caused by pathogens that reside in biofilms, we sought to investigate how biofilms influence the evolution of antibiotic resistance. We hypothesize that the inherent spatial structure of biofilms facilitates the accumulation and persistence of spontaneously evolved antibiotic‐resistant mutants. To test this, we tracked the frequency of mutants resistant to kanamycin and rifampicin in biofilm populations of Escherichia coli before, during, and after an antibiotic treatment regimen. Our results show that biofilms accumulate resistant mutants even in the absence of antibiotics. This resistance was found to be heritable and thus unlike the phenotypic plasticity of so‐called “persister cells” that have been shown to occur in biofilms. Upon exposure to an antibiotic, resistant mutants swept to high frequency. Following the conclusion of treatment, these resistant mutants remained at unexpectedly high frequencies in the biofilms for over 45 days. In contrast, when samples from kanamycin‐treated biofilms were used to found well‐mixed liquid cultures and propagated by serial transfer, the frequency of resistant cells dramatically decreased as they were outcompeted by sensitive clones. These observations suggest that the emergence of antibiotic resistance through spontaneous mutations in spatially structured biofilms may significantly contribute to the emergence and persistence of mutants that are resistant to antibiotics used to treat bacterial infections.
    Sponsors
    MF was supported by a fellowship from the Bioinformatics and Computational Biology Graduate Program at the University of Idaho.
    Keyword
    adaptation
    antibiotic resistance
    bacteria
    biofilm
    selection
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058927345&doi=10.1111%2feva.12728&partnerID=40&md5=7c974e14859aaa4a123d9a1b704ce0ab; http://hdl.handle.net/10713/10244
    ae974a485f413a2113503eed53cd6c53
    10.1111/eva.12728
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