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首页> 外文期刊>Environmental toxicology and chemistry >MECHANISTIC LINK BETWEEN UPTAKE OF SULFONAMIDES AND BACTERIOSTATIC EFFECT: MODEL DEVELOPMENT AND APPLICATION TO EXPERIMENTAL DATA FROM TWO SOIL MICROORGANISMS
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MECHANISTIC LINK BETWEEN UPTAKE OF SULFONAMIDES AND BACTERIOSTATIC EFFECT: MODEL DEVELOPMENT AND APPLICATION TO EXPERIMENTAL DATA FROM TWO SOIL MICROORGANISMS

机译：磺酰胺类药物的吸收与抑菌作用的机理联系：两种土壤微生物实验数据的模型开发和应用

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摘要

Sulfonamides (SA) are antibiotic compounds that are widely used as human and veterinary pharmaceuticals. They are not rapidly biodegradable and have been detected in various environmental compartments. Effects of sulfonamides on microbial endpoints in soil have been reported from laboratory incubation studies. Sulfonamides inhibit the growth of sensitive microorganisms by competitive binding to the dihydropteroate-synthase (DHPS) enzyme of folic acid production. A mathematical model was developed that relates the extracellular SA concentration to the inhibition of the relative bacterial growth rate. Two factors-the anionic accumulation factor (AAF) and the cellular affinity factor (CAF)-determine the effective concentration of an SA. The AAF describes the SA uptake into bacterial cells and varies with both the extra- and intracellular pH values and with the acidic pK_a value of an SA. The CAF subsumes relevant cellular and enzyme properties, and is directly proportional to the DHPS affinity constant for an SA. Based on the model, a mechanistic dose-response relationship is developed and evaluated against previously published data, where differences in the responses of Pseudomonas aeruginosa and Panthoea agglomerans toward changing medium pH values were found, most likely as a result of their diverse pH regulation. The derived dose-response relationship explains the pH and pK_a dependency of mean effective concentration values (EC50) of eight SA and two soil bacteria based on AAF and CAF values. The mathematical model can be used to extrapolate sulfonamide effects to other pH values and to calculate the CAF as a pH-independent measure for the SA effects on microbial growth.
机译：磺酰胺（SA）是被广泛用作人类和兽药的抗生素化合物。它们不能快速生物降解，并且已经在各种环境隔室中被检测到。实验室培养研究已经报道了磺酰胺对土壤中微生物终点的影响。磺酰胺通过竞争性结合叶酸的二氢蝶呤合成酶（DHPS）酶来抑制敏感微生物的生长。建立了数学模型，该模型将细胞外SA浓度与相对细菌生长速率的抑制相关。阴离子积累因子（AAF）和细胞亲和因子（CAF）这两个因素决定了SA的有效浓度。 AAF描述了SA进入细菌细胞的过程，并随细胞外和细胞内pH值以及SA的酸性pK_a值而变化。 CAF包含相关的细胞和酶特性，并且与SA的DHPS亲和常数成正比。基于该模型，建立了机械剂量-反应关系，并根据以前发表的数据进行了评估，在该数据中发现了铜绿假单胞菌和聚结球菌对中等pH值变化的响应差异，这很可能是由于其不同的pH调节作用所致。推导的剂量反应关系解释了基于AAF和CAF值的8种SA和两种土壤细菌的平均有效浓度值（EC50）的pH和pK_a依赖性。该数学模型可用于将磺酰胺作用外推至其他pH值，并计算CAF作为SA对微生物生长的影响的pH无关度量。

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  • 来源
    《Environmental toxicology and chemistry》 |2010年第7期|P.1445-1452|共8页
  • 作者

    Andreas Focks; Joerg Klasmeier; Michael Matthies;

  • 作者单位

    University of Osnabrueck, Institute of Environmental Systems Research, Barbarastrasse 12, 49069 Osnabrueck, Germany;

    rnUniversity of Osnabrueck, Institute of Environmental Systems Research, Barbarastrasse 12, 49069 Osnabrueck, Germany;

    rnUniversity of Osnabrueck, Institute of Environmental Systems Research, Barbarastrasse 12, 49069 Osnabrueck, Germany;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    sulfonamides; soil microbes; effect model; dose-response relationship; pH dependence;

    机译：磺酰胺;土壤微生物;效果模型剂量反应关系pH依赖性;

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