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Author: search.filters.author.Barbara E. MurraySubject: search.filters.subject.endocarditis

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    Item type:Publication,
    Correlation between Mutations in
    <i>liaFSR</i>
    of Enterococcus faecium and MIC of Daptomycin: Revisiting Daptomycin Breakpoints
    (2012)
    MUNITA SEPULVEDA, JOSE MANUEL  
    ;
    Diana Panesso
    ;
    Lorena Diaz
    ;
    Truc T. Tran
    ;
    Jinnethe Reyes
    Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 μg/ml (the DAP breakpoint is 4 μg/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 μg/ml might harbor mutations in liaFSR, we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 μg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 μg/ml), 5 had mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC of ≤2 μg/ml harbored mutations in this system (P<0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of ≥16 μg/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated
      14Scopus© Citations 104
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    Item type:Publication,
    A liaF Codon Deletion Abolishes Daptomycin Bactericidal Activity against Vancomycin-Resistant Enterococcus faecalis
    (2013)
    MUNITA SEPULVEDA, JOSE MANUEL  
    ;
    Truc T. Tran
    ;
    Lorena Diaz
    ;
    Diana Panesso
    ;
    Jinnethe Reyes
    The genetic bases for antibiotic tolerance are obscure. Daptomycin (DAP) is a lipopeptide antibiotic with bactericidal activity against enterococci. Using time-kill assays, we provide evidence for the first time that a deletion of isoleucine in position 177 of LiaF, a member of the three-component regulatory system LiaFSR involved in the cell envelope response to antimicrobials, is directly responsible for a DAP-tolerant phenotype and is likely to negatively affect response to DAP therapy.
      4Scopus© Citations 66
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    Item type:Publication,
    What's New in the Treatment of Enterococcal Endocarditis?
    (2014)
    Masayuki Nigo
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    ;
    Cesar A. Arias
    ;
    Barbara E. Murray
      27Scopus© Citations 49