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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Correlation between mutations in liaFSR of enterococcus faecium and MIC of daptomycin: Revisiting daptomycin breakpoints
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Correlation between mutations in liaFSR of enterococcus faecium and MIC of daptomycin: Revisiting daptomycin breakpoints

机译：粪肠球菌liaFSR突变与达托霉素MIC的相关性：重新探讨达托霉素的断点

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摘要

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.
机译：liaFSR的突变是一种控制细胞包膜应力反应的三组分调节系统，最近与肠球菌中达托霉素（DAP）耐药性的出现有关。我们以前的工作表明liaF突变使耐万古霉素的粪肠球菌菌株的DAP MIC从1增加到3μg/ ml（DAP断点是4μg/ ml），这表明liaFSR系统中的突变可能是关键的初始DAP耐药性发展中发生的事件。基于DFS MIC在3至4μg/ ml之间的临床肠球菌分离株可能在liaFSR中携带突变的假设，我们在Mueller-Hinton的Etest中研究了38株肠球菌粪便血流分离株，其中8株DAP MIC在3-4μg/ ml之间。琼脂有趣的是，这8个分离株中有6个预测了LiaFSR系统中的氨基酸变化。此外，我们先前显示了在6种抗DAP的屎肠球菌分离株（MIC> 4μg/ ml）中，有5种在liaFSR中具有突变。相反，在此系统中，DAP MIC≤2μg/ ml的16种粪肠球菌都没有突变（P <0.0001）。除一个具有liaFSR变化的分离株外，使用脑心浸液琼脂（BHIA）进行Etest测得的DAP MIC≥16μg/ ml，该培养基可更好地支持肠球菌生长。我们的研究结果提供了较高敏感性范围内的DAP MIC与liaFSR系统中的突变之间的强烈关联。在BHIA上进行的敏感性测试可能有助于鉴定这些粪肠球菌的第一步突变体。我们的结果还表明，可能需要重新评估屎肠球菌的当前DAP断点。

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