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基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立

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梁丽营, 曾鸿鹄, 龙茜, 孙昊宇, 林志芬, 莫凌云. 基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立[J]. 环境化学, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
引用本文: 梁丽营, 曾鸿鹄, 龙茜, 孙昊宇, 林志芬, 莫凌云. 基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立[J]. 环境化学, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
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LIANG Liying, ZENG Honghu, LONG Xi, SUN Haoyu, LIN Zhifen, MO Lingyun. Establishment of a QSAR model based on the joint effects of quorum sensing inhibitors and sulfonamides on Escherichia Coli[J]. Environmental Chemistry, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
Citation: LIANG Liying, ZENG Honghu, LONG Xi, SUN Haoyu, LIN Zhifen, MO Lingyun. Establishment of a QSAR model based on the joint effects of quorum sensing inhibitors and sulfonamides on Escherichia Coli[J]. Environmental Chemistry, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
shu

基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立

  • 1.

    桂林理工大学环境科学与工程学院, 桂林, 541004;

  • 2.

    污染控制与资源化研究国家重点实验室, 同济大学环境科学与工程学院, 上海, 200092

  • 基金项目:

    同济大学污染控制与资源化研究国家重点实验室自主研究（重点）项目（PCRRY11003），国家自然科学基金（21377096，21577105）和同济大学英才（攀登）计划（0400219287）资助.

Establishment of a QSAR model based on the joint effects of quorum sensing inhibitors and sulfonamides on Escherichia Coli

  • 1.

    College of Environmental Science and Engineering, Guilin University of Technology, Guilin, 541004, China;

  • 2.

    State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China

  • Fund Project: Supporded by the Foundation of the State Key Laboratory of Pollution Control and Resource Reuse, China(PCRRY11003), the National Natural Science Foundation of China(21377096, 21577105), the "Climbing" Program of Tongji University(0400219287).

  • 摘要: 以大肠杆菌为模式生物，分别测定了7种磺胺（SAs，分别为磺胺二甲基嘧啶（SCP）、磺胺吡啶（SPY）、磺胺甲恶唑（SMX）、周效磺胺（SDX）、磺胺喹恶磷（SQ）、磺胺对甲氧嘧啶（SM）、磺胺甲氧哒嗪（SMP）），及3种群体感应抑制剂（QSIs，分别为3-甲基-2-（5H）-呋喃酮（MF）、N-乙烯基吡咯烷酮（VP）、（R）-3-吡咯烷醇（HPL））的单一毒性和联合毒性，并且采用分子对接技术建立了QSIs与SAs对大肠杆菌联合毒性的QSAR模型.结果表明其联合毒性效应表现为拮抗和相加作用；同时，基于SAs和QSIs分别与它们的目标靶蛋白二氢叶酸合成酶（DHP5）与大肠杆菌家族蛋白（SdiA）之间相互作用的结合能（Ebinding）和混合物的辛醇-水分配系数Kow（mix）构建了SAs和QSIs对大肠杆菌的二元联合毒性的QSAR模型，具有较好的相关性（R2为0.901）.该模型经过验证，具有良好的预测能力（预测值与实测值的R2为0.913），研究可为今后抗生素与群体感应抑制剂的环境联合生态风险评价以及毒性预测提供一定的理论依据和技术支持.
    Abstract: Single and combined toxicity of seven sulfonamides (SAs) and three quorum sensing inhibitors (QSIs) were measured on the model organism E. coli. The results showed that their joint toxic actions were antagonism and addition. In addition, molecular docking was used to calculate the Ebinding value by stimulating the interactions of SAs and QSIs with Dihydro folate synthase (DPHs) and E. coli fami protein SdiA. Based on the Ebinding value and the octanol-water partition coefficient Kow(mix), the QSAR model of joint effects of SAs and QSIs was established with a good correlation (R2=0.901). The work can provide a theoretical basis and technical support on the ecological risk assessment and prediction of joint effects of SAs and QSIs.
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  • [1] ARIAS C A. MURRAY B E. Antibiotic-resistant bugs in the 21st century-A clinical super-challenge[J]. New England Journal of Medicine, 2009, 360(5):439-443.
    [2] 沈群辉,冀秀玲,傅淑珺,等.黄浦江水域抗生素及抗性基因污染初步研究[J]. 生态环境学报,2012,21(10):1717-1723.

    SHEN Q H, JI X L, FU S J, et al. Preliminary studies on the pollution levels of antibiotic and antibiotic resistance genes in Huangpu River, China[J]. Ecology and Environmental Sciences, 2012, 21(10):1717-1723(in Chinese).

    [3] 何基兵,胡安谊,陈猛,等.九龙江河口及厦门污水处理设施抗生素抗性基因污染分析[J]. 微生物学通报,2012,39(5):683-695.

    HE J B, HU A Y, CHEN M, et al. Studies on the pollution levels of antibiotic resistance genes in Jiulong River estuary and wastewater treatment plants in Xiamen[J]. Microbiology China,2012,39(5):683-695(in Chinese).

    [4] 乔敏,吴楠.土壤环境中四环素类抗生素残留及抗性基因污染的研究进展[J]. 生态毒理学报,2010,5(5):618-627.

    QIAO M, WU N. Tetracycline residues and tetracycline resistance gene pollution in soil:A review[J].Asian Journal of Ecotoxicology,2010,5(5):618-627(in Chinese).

    [5] 郭嘉亮,陈卫民.细菌群体感应信号分子与抑制剂研究进展[J]. 生命科学,2007,2(2):224-232.

    GUO J L, CHEN W M. Bacterial sensing signal molecule inhibitor group and progress[J]. Life Sciences, 2007,2(2):224-232(in Chinese).

    [6] 安情情,姚志峰,顾宇菲,等.磺胺类抗生素与群体感应抑制剂对发光菌的联合毒性及其机制初探[J]. 环境化学,2014,33(12):2068-2075.

    AN Q Q, YAO Z F, GU Y F, et al. Joint effects and mechanisms of binary toxicity of sulfa antibiotics and quorum sensing inhibitors to Vibrio fischeri[J]. Environment Chemistry,2014,33(12):2068-2075(in Chinese).

    [7] 刘灿,葛鸿铭,龙茜,等.磺胺与群感抑制剂对大肠杆菌的联合毒性机制初探[J]. 环境化学,2015,34(10):1854-1859.

    LIU C,GE H M,LONG X,et al.A preliminary investigation on the mechanism of binary mixture toxicity containing sulfonamides and quorum sensing inhibitors on Escherichia coli[J]. Environmental Chemistry,2015,34(10):1854-1859(in Chinese).

    [8] 张栩嘉.应用结构分类方法研究有机污染物种间毒性作用机理[D]. 吉林:东北师范大学博士学位论文,2013:2-6. ZHANG S J, Interspecies mechanisms study of toxic action for organic pollutants using structure classification method[D]. Jilin:Northeast Normal University PhD Thesis, 2013:2

    -6(in Chinese).

    [9]
    [10]
    [11] 秦红,陈景文,王莹,等.有机污染物生物富集因子定量预测模型的建立与评价[J]. 科学通报,2009,54(1):27-32.

    QIN H, CHEN J W, WANG Y, et al. Development and assessment of quantitative structure-activity relationship models for bioconcentration factors of organic pollutants[J]. Chinese Science Bulletin, 2009, 54(1):27-32(in Chinese).

    [12] 葛燕丽,张兵,程瑾,等.芳基磺胺类γ-分泌酶抑制剂的三维定量构效关系研究[J]. 计算机与应用化学,2010,27(4):475-479.

    GE Y L, ZHANG B, CHENG J, et al. Study on 3D-QSAR of arylsulfonamides as γ-secretase inhibitors[J]. Computers and Applied Chemistry, 2010,27(4):475-479(in Chinese).

    [13]
    [14] DENG Z Q, LIN Z F, ZOU X M, et al. Model of hormesis and its toxicity mechanism based on quorum sensing:a case study on the toxicity of sulfonamides to photobacterium phosphoreum[J]. Environmental Science & Technology, 2012, 46(14):7746-7754.
    [15] ZOU X M, ZHOU X H, LIN Z F, et al. A docking-based receptor library of antibiotics and its novel application in predicting chronic mixture toxicity for environmental risk assessment[J]. Environmental Monitoring and Assessment, 2013, 185(6):4513-4527.
    [16] GOLBRAIKH A, TROPSHA A. Beware of q2![J]. J Mol Graph Model, 2002, 20(4):269-276.
    [17] 王斌,余刚,张祖麟,等.烷基醇化合物的定量结构活性相关及联合毒性预测[J]. 科学通报, 2006,51(13):1513-1518.

    WANG B, YU G, ZHANG Z L, et al. Quantitative structure activity alkyl alcohol compound and related joint toxicity prediction[J]. Chinese Science Bulletin,2006,51(13):513-1518(in Chinese).

    [18] WU G S, ROBERTSON D H, BROOKS C L, et al. Detailed analysis of grid-based molecular docking:a case study of CDOCKER-A CHARMm-based MD docking algorithm[J]. Journal of Computational Chemistry, 2003, 24(13):1549-1562.
    [19] SUN H Y, GE H M, ZHENG M, et al. Mechanism underlying time-dependent cross-phenomenon between concentration-response curves and concentration addittion curves:A case study of sulfonamides-erythromycin mixture on Escherichia Coli[J]. Scientific Resports, 2016:1-10.
    [20] KÖNEMANN H. Quantitative structure-activity relationships in fish toxicity studies Part 1:Relationship for 50 industrial pollutants[J]. Toxicology, 1981, 19(3):209-221.
    [21] LIN Z F, YU H X, WEI D B, et al. Prediction of mixture toxicity with its total hydrophobicity[J]. Chemosphere, 2002,46(2):305-310.
    [22] ZENG M, LIN Z F, YIN D Q, et al. QSAR for predicting joint toxicity of halogenated benzenes to dicrateria zhanjiangensis[J]. Bulletin of Environmental Contamination and Toxicology, 2008,81(6):525-530.
    [23] ZARFL C, MATTHIES M, KLASMEIER J. A mechanistical model for the uptake of sulfonamides by bacteria[J]. Chemosphere, 2008,70(5):753-760.
    [24]
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  • 收稿日期:  2016-05-31
  • 刊出日期:  2017-01-15
梁丽营, 曾鸿鹄, 龙茜, 孙昊宇, 林志芬, 莫凌云. 基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立[J]. 环境化学, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
引用本文: 梁丽营, 曾鸿鹄, 龙茜, 孙昊宇, 林志芬, 莫凌云. 基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立[J]. 环境化学, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
shu
LIANG Liying, ZENG Honghu, LONG Xi, SUN Haoyu, LIN Zhifen, MO Lingyun. Establishment of a QSAR model based on the joint effects of quorum sensing inhibitors and sulfonamides on Escherichia Coli[J]. Environmental Chemistry, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
Citation: LIANG Liying, ZENG Honghu, LONG Xi, SUN Haoyu, LIN Zhifen, MO Lingyun. Establishment of a QSAR model based on the joint effects of quorum sensing inhibitors and sulfonamides on Escherichia Coli[J]. Environmental Chemistry, 2017, 36(1): 92-99. doi: 10.7524/j.issn.0254-6108.2017.01.2016053102
shu

基于群体感应抑制剂与磺胺对大肠杆菌联合毒性效应的QSAR模型建立

  • 1.  桂林理工大学环境科学与工程学院, 桂林, 541004;
  • 2.  污染控制与资源化研究国家重点实验室, 同济大学环境科学与工程学院, 上海, 200092
  • 收稿日期:  2016-05-31
基金项目:

同济大学污染控制与资源化研究国家重点实验室自主研究（重点）项目（PCRRY11003），国家自然科学基金（21377096，21577105）和同济大学英才（攀登）计划（0400219287）资助.

摘要: 以大肠杆菌为模式生物，分别测定了7种磺胺（SAs，分别为磺胺二甲基嘧啶（SCP）、磺胺吡啶（SPY）、磺胺甲恶唑（SMX）、周效磺胺（SDX）、磺胺喹恶磷（SQ）、磺胺对甲氧嘧啶（SM）、磺胺甲氧哒嗪（SMP）），及3种群体感应抑制剂（QSIs，分别为3-甲基-2-（5H）-呋喃酮（MF）、N-乙烯基吡咯烷酮（VP）、（R）-3-吡咯烷醇（HPL））的单一毒性和联合毒性，并且采用分子对接技术建立了QSIs与SAs对大肠杆菌联合毒性的QSAR模型.结果表明其联合毒性效应表现为拮抗和相加作用；同时，基于SAs和QSIs分别与它们的目标靶蛋白二氢叶酸合成酶（DHP5）与大肠杆菌家族蛋白（SdiA）之间相互作用的结合能（Ebinding）和混合物的辛醇-水分配系数Kow（mix）构建了SAs和QSIs对大肠杆菌的二元联合毒性的QSAR模型，具有较好的相关性（R2为0.901）.该模型经过验证，具有良好的预测能力（预测值与实测值的R2为0.913），研究可为今后抗生素与群体感应抑制剂的环境联合生态风险评价以及毒性预测提供一定的理论依据和技术支持.

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