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dc.contributor.authorMiller, Corwin
Kong, Jiayi
Tran, Truc T.
Arias, Cesar A.
Saxer, Gerda
Shamoo, Yousif
dc.date.accessioned 2014-10-06T17:18:03Z
dc.date.available 2014-10-06T17:18:03Z
dc.date.issued 2013
dc.identifier.citation Miller, Corwin, Kong, Jiayi, Tran, Truc T., et al.. "Adaptation of Enterococcus faecalis to Daptomycin Reveals an Ordered Progression to Resistance." Antimicrobial Agents and Chemotherapy, 57, no. 11 (2013) American Society for Microbiology: 5373-5383. http://dx.doi.org/10.1128/AAC.01473-13.
dc.identifier.urihttps://hdl.handle.net/1911/77403
dc.description.abstract With increasing numbers of hospital-acquired antibiotic resistant infections each year and staggering health care costs, there is a clear need for new antimicrobial agents, as well as novel strategies to extend their clinical efficacy. While genomic studies have provided a wealth of information about the alleles associated with adaptation to antibiotics, they do not provide essential information about the relative importance of genomic changes, their order of appearance, or potential epistatic relationships between adaptive changes. Here we used quantitative experimental evolution of a single polymorphic population in continuous culture with whole-genome sequencing and allelic frequency measurements to study daptomycin (DAP) resistance in the vancomycin-resistant clinical pathogen Enterococcus faecalis S613. Importantly, we sustained both planktonic and nonplanktonic (i.e., biofilm) populations in coculture as the concentration of antibiotic was raised, facilitating the development of more ecological complexity than is typically observed in laboratory evolution. Quantitative experimental evolution revealed a clear order and hierarchy of genetic changes leading to resistance, the signaling and metabolic pathways responsible, and the relative importance of these mutations to the evolution of DAP resistance. Despite the relative simplicity of this ex vivo approach compared to the ecological complexity of the human body, we showed that experimental evolution allows for rapid identification of clinically relevant adaptive molecular pathways and new targets for drug design in pathogens.
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.title Adaptation of Enterococcus faecalis to Daptomycin Reveals an Ordered Progression to Resistance
dc.type Journal article
dc.contributor.funder National Institutes of Health, National Institute of Allergy and Infectious Diseases
dc.contributor.funder National Institutes of Health
dc.contributor.funder John S. Dunn Foundation
dc.citation.journalTitle Antimicrobial Agents and Chemotherapy
dc.citation.volumeNumber 57
dc.citation.issueNumber 11
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1128/AAC.01473-13
dc.identifier.pmcid PMC3811304
dc.identifier.pmid 23959318
dc.identifier.grantID R01 AI080714 (National Institutes of Health, National Institute of Allergy and Infectious Diseases)
dc.identifier.grantID HDTRA1010-0069 (National Institutes of Health)
dc.identifier.grantID R01 AI093749 (National Institutes of Health, National Institute of Allergy and Infectious Diseases)
dc.identifier.grantID Collaborative Research Award (John S. Dunn Foundation)
dc.type.publication publisher version
dc.citation.firstpage 5373
dc.citation.lastpage 5383


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