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High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction

机译:高通量筛选,以鉴定微生物硫酸盐还原的有效和特定抑制剂

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摘要

The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to identify potent and selective inhibitors of SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Zinc pyrithione is the most potent inhibitor of sulfidogenesis that we identified, and is several orders of magnitude more potent than commonly used industrial biocides. Both zinc and copper pyrithione are also moderately selective against SRM. The high-throughput (HT) approach we present can be readily adapted to target SRM in diverse environments and similar strategies could be used to quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant to efforts to engineer environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.
机译:复杂微生物生态系统的选择性扰动可预测地影响工程和工业环境中的结果,这仍然是地球微生物学的巨大挑战。在某些工业生态系统中,例如储油库中,硫酸盐还原微生物(SRM)产生有毒,易爆和腐蚀性的硫化氢。尽管产生硫化物的经济成本很高,但对可能的抑制性化合物的化学空间的探索却很少,而且很少有工作定量评估推定的酸化处理的选择性。我们已经开发出一种高通量筛选策略,以鉴定SRM的有效和选择性抑制剂,定量排名数百种化合物的选择性和效力,并鉴定以前无法识别的SRM选择性抑制剂和抑制剂之间的协同相互作用。巯氧吡啶锌是我们确定的最有效的硫化物抑制剂,并且比常用的工业杀菌剂强几个数量级。巯氧吡啶锌和巯氧吡啶铜也对SRM具有中等选择性。我们目前提出的高通量(HT)方法可以很容易地适应各种环境中的SRM靶标,并且可以使用相似的策略来量化各种微生物代谢抑制剂的效价和选择性。我们的发现和方法与工程环境生态系统的努力以及了解自然梯度在塑造微生物生态位空间中的作用有关。

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  • 来源
    《Environmental Science & Technology》 |2017年第12期|7278-7285|共8页
  • 作者单位

    Energy Biosciences Institute, University of California, Berkeley, Berkeley, California 94720, United States,Physical Biosciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, United States;

    Energy Biosciences Institute, University of California, Berkeley, Berkeley, California 94720, United States;

    Energy Biosciences Institute, University of California, Berkeley, Berkeley, California 94720, United States;

    Small Molecule Discovery Center, University of California, San Francisco, San Francisco, California 94143, United States;

    Small Molecule Discovery Center, University of California, San Francisco, San Francisco, California 94143, United States;

    Energy Biosciences Institute, University of California, Berkeley, Berkeley, California 94720, United States,Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States,Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California 94720, United States;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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