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首页> 外文期刊>RSC Advances >Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes
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Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

机译：肠球菌的膜适应局限性粪便底部敏感性和无法对共轭低电解质产生显着抗性的影响

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摘要

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4-16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.
机译：抗生素抗性细菌的越来越多的问题，以及新的抗生素的缺乏，重定向对寻找替代抗微生物剂的关注。缀合的寡核电解质（CoES）是一种新一类的抗微生物剂，其插入细菌细胞膜并抑制抗革兰氏阳性和革兰氏阴性细菌。在这项研究中，研究了肠球菌粪便培养的Coe抵抗程度。肠球菌能够在敌对环境中生长，并在临床环境中造成靶向抗生素的抗生素等膜的抵抗力。在此，我们通过开发E. valeals OG1RF的Coe抗性菌株来扩大COE的抗微生物作用机制的知识。进化研究产生了相对于野生型抗微生物抗性的4-16倍的菌株。耐抗性与LiaFSR操纵子相关的累积剂特异性突变，这是一种细胞包膜相关的应力 - 反应传感和调节系统。 CoE抗性分离物显示出显着改变的膜脂肪酸组合物。随后，与单一脂肪酸的外源补充，基于主导突变体的脂肪酸谱的那些，野生型E.粪便抗性的抗性增加。组合，遗传，脂肪酸和吸收研究支持通过插入和破坏膜的假设，使得这种发生的机制是特异于破坏剂。这些结果是通过一系列生物物理实验验证，所述生物物理实验显示CoEs积累和扰动适应膜提取物的趋势。统称，CoES是靶向E.粪便的抗微生物剂的数据支持，并且对膜重塑的生物学限制受到影响的严重抗性菌株的出现具有很大的障碍，这可能发生在大肠杆菌中。

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  • 来源
    《RSC Advances》 |2018年第19期|共10页
  • 作者

    Chilambi Gayatri Shankar; Gao Iris H.; Yoon Bo Kyeong; Park Soohyun; Kawakami Lisa M.; Ravikumar Vikashini; Chan-Park Mary B.; Cho Nam-Joon; Bazan Guillermo C.; Kline Kimberly A.; Rice Scott A.; Hinks Jamie;

  • 作者单位

    Nanyang Technol Univ Interdisciplinary Grad Sch Singapore 637141 Singapore;

    Nanyang Technol Univ SCELSE Singapore 637551 Singapore;

    Nanyang Technol Univ Sch Mat Sci &

    Engn 50 Nanyang Ave Singapore 639798 Singapore;

    Nanyang Technol Univ Sch Mat Sci &

    Engn 50 Nanyang Ave Singapore 639798 Singapore;

    Nanyang Technol Univ Sch Mat Sci &

    Engn 50 Nanyang Ave Singapore 639798 Singapore;

    Nanyang Technol Univ SCELSE Singapore 637551 Singapore;

    Nanyang Technol Univ Sch Chem &

    Biomed Engn Singapore 637459 Singapore;

    Nanyang Technol Univ Sch Mat Sci &

    Engn 50 Nanyang Ave Singapore 639798 Singapore;

    Nanyang Technol Univ Sch Chem &

    Biomed Engn Singapore 637459 Singapore;

    Nanyang Technol Univ SCELSE Singapore 637551 Singapore;

    Nanyang Technol Univ SCELSE Singapore 637551 Singapore;

    Nanyang Technol Univ SCELSE Singapore 637551 Singapore;

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  • 正文语种 eng
  • 中图分类 化学;
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