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A liaR deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant Enterococcus faecalis

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dc.contributor.author Reyes, Jinnethe
dc.contributor.author Panesso, Diana
dc.contributor.author Mishra, Nagendra
dc.contributor.author Cruz, Melissa
dc.contributor.author Munita, José
dc.contributor.author Singh, Kavindra
dc.contributor.author Yeaman, Michael
dc.contributor.author Murray, Barbara
dc.contributor.author Shamoo, Yousif
dc.contributor.author Garsin, Danielle
dc.contributor.author Bayer, Arnold
dc.contributor.author Arias, César A.
dc.date.accessioned 2016-05-23T14:28:53Z
dc.date.available 2016-05-23T14:28:53Z
dc.date.issued 2015
dc.identifier.citation Journal of Infectious Diseases, April 2015, vol. 211, n°8, p.1317-1325 es_CL
dc.identifier.uri http://dx.doi.org/10.1093/infdis/jiu602 es_CL
dc.identifier.uri http://hdl.handle.net/11447/307
dc.description.abstract Daptomycin is a lipopeptide antibiotic that is used clinically against many gram-positive bacterial pathogens and is considered a key frontline bactericidal antibiotic to treat multidrug-resistant enterococci. Emergence of daptomycin resistance during therapy of serious enterococcal infections is a major clinical issue. In this work, we show that deletion of the gene encoding the response regulator, LiaR (a member of the LiaFSR system that controls cell envelope homeostasis), from daptomycin-resistant Enterococcus faecalis not only reversed resistance to 2 clinically available cell membrane-targeting antimicrobials (daptomycin and telavancin), but also resulted in hypersusceptibility to these antibiotics and to a variety of antimicrobial peptides of diverse origin and with different mechanisms of action. The changes in susceptibility to these antibiotics and antimicrobial peptides correlated with in vivo attenuation in a Caenorhabditis elegans model. Mechanistically, deletion of liaR altered the localization of cardiolipin microdomains in the cell membrane. Our findings suggest that LiaR is a master regulator of the enterococcal cell membrane response to diverse antimicrobial agents and peptides; as such, LiaR represents a novel target to restore the activity of clinically useful antimicrobials against these organisms and, potentially, increase susceptibility to endogenous antimicrobial peptides. es_CL
dc.language.iso en_US es_CL
dc.publisher The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America es_CL
dc.subject E. faecalis es_CL
dc.subject LiaFSR es_CL
dc.subject Antimicrobial peptides es_CL
dc.subject Daptomycin es_CL
dc.title A liaR deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant Enterococcus faecalis es_CL
dc.type Artículo es_CL


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