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    Disrupting membrane adaptation restores in vivo efficacy of antibiotics against multidrug-resistant enterococci and potentiates killing by human neutrophils

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    TY - GEN T1 - Disrupting membrane adaptation restores in vivo efficacy of antibiotics against multidrug-resistant enterococci and potentiates killing by human neutrophils UR - http://hdl.handle.net/20.500.12495/2650 PB - Oxford University Press AB - ER - @misc{20.500.12495_2650, author = {}, title = {Disrupting membrane adaptation restores in vivo efficacy of antibiotics against multidrug-resistant enterococci and potentiates killing by human neutrophils}, year = {}, abstract = {}, url = {http://hdl.handle.net/20.500.12495/2650} }RT Generic T1 Disrupting membrane adaptation restores in vivo efficacy of antibiotics against multidrug-resistant enterococci and potentiates killing by human neutrophils LK http://hdl.handle.net/20.500.12495/2650 PB Oxford University Press AB OL Spanish (121)
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    Author
    Rincon Núñez, Sandra 
    Panesso, Diana 
    Miller, William R
    Singh, Kavindra V
    Cruz, Melissa R
    Khan, Ayesha
    Dinh, An Q
    Diaz, Lorena
    Rios, Rafael
    Shamoo, Yousif
    Reyes, Jinnethe
    Tran, Truc T
    Garsin, Danielle A
    Arias, Cesar A
    Published in
    Journal of Infectious Diseases, 0022-1899, Vol 220, Num 3, 2019, Pag 494–504
    Published for
    Oxford University Press
    URI
    http://hdl.handle.net/20.500.12495/2650
    Source's URL
    https://academic.oup.com/jid/article-abstract/220/3/494/5425477?redirectedFrom=fulltext
    DOI
    https://doi.org/10.1093/infdis/jiz131

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    Abstract
    Daptomycin resistance in enterococci is often mediated by the LiaFSR system, which orchestrates the cell membrane stress response. Activation of LiaFSR through the response regulator LiaR generates major changes in cell membrane function and architecture (membrane adaptive response), permitting the organism to survive the antibiotic attack. Here, using a laboratory strain of Enterococcus faecalis, we developed a novel Caenorhabditis elegans model of daptomycin therapy and showed that disrupting LiaR-mediated cell membrane adaptation restores the in vivo activity of daptomycin. The LiaR effect was also seen in a clinical strain of daptomycin-resistant Enterococcus faecium, using a murine model of peritonitis. Furthermore, alteration of the cell membrane response increased the ability of human polymorphonuclear neutrophils to readily clear both E. faecalis and multidrug-resistant E. faecium. Our results provide proof of concept that targeting the cell membrane adaptive response restores the in vivo activity of antibiotics, prevents resistance, and enhances the ability of the innate immune system to kill infecting bacteria.
    Keywords
    LiaR
    Daptomycin
    Caenorhabditis elegans
    PMNs
    Phagocytosis
    Topics
    Estrés
    Daptomicina
    Farmacorresistencia microbiana
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