新型抗菌剂——群体感应抑制剂与传统抗菌剂对大肠杆菌的联合毒性效应

刘艺楠, 孙昊宇, 沈洪艳, 林志芬. 新型抗菌剂——群体感应抑制剂与传统抗菌剂对大肠杆菌的联合毒性效应[J]. 环境化学, 2020, (4): 941-949. doi: 10.7524/j.issn.0254-6108.2019040104
引用本文: 刘艺楠, 孙昊宇, 沈洪艳, 林志芬. 新型抗菌剂——群体感应抑制剂与传统抗菌剂对大肠杆菌的联合毒性效应[J]. 环境化学, 2020, (4): 941-949. doi: 10.7524/j.issn.0254-6108.2019040104
LIU Yinan, SUN Haoyu, SHEN Hongyan, LIN Zhifen. Combined toxicities of a new antimicrobials-quorum sensing inhibitors and traditional antimicrobials against Escherichia coli[J]. Environmental Chemistry, 2020, (4): 941-949. doi: 10.7524/j.issn.0254-6108.2019040104
Citation: LIU Yinan, SUN Haoyu, SHEN Hongyan, LIN Zhifen. Combined toxicities of a new antimicrobials-quorum sensing inhibitors and traditional antimicrobials against Escherichia coli[J]. Environmental Chemistry, 2020, (4): 941-949. doi: 10.7524/j.issn.0254-6108.2019040104

新型抗菌剂——群体感应抑制剂与传统抗菌剂对大肠杆菌的联合毒性效应

    通讯作者: 沈洪艳, E-mail: shy0405@sina.com
  • 基金项目:

    国家自然科学基金(41373096,21577105,21777123),国家环保公益课题(201509041-05),河北省自然科学基金(B2014208068),河北省药用分子化学实验室开放基金,河北省环保厅公益课题,河北省重点学科建设基金,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(PCRRK16007),水体污染控制与治理科技重大专项(2018ZX07109-1),上海市科学技术委员会科研计划课题(17DZ1200103,14DZ2261100),环境化学与生态毒理学国家重点实验室开放基金课题(KF2016-11)和111工程资助.

Combined toxicities of a new antimicrobials-quorum sensing inhibitors and traditional antimicrobials against Escherichia coli

    Corresponding author: SHEN Hongyan, shy0405@sina.com
  • Fund Project: Supported by the National Natural Science Foundation of China (41373096,21577105,21777123), National Environmental Protection Project (201509041-05), Hebei Province Natural Science Fundation (B2014208068), Hebei Province Pharmaceutical Molecular Chemistry Laboratory Open Foundation, Hebei Province Environmental Protection Public Interest Project, and Hebei Province Key Disciplines Construction Fund Project, the Foundation of the State Key Laboratory of Pollution Control and Resource Reuse, China (PCRRK16007), the National Water Pollution Control and Treatment Science and Technology Major Project of China (2018ZX07109-1), the Science & Technology Commission of Shanghai Municipality (17DZ1200103,14DZ2261100), the State Key Laboratory of Environmental Chemistry and Ecotoxicology (KF2016-11) and the 111 Project.
  • 摘要: 群体感应抑制剂(QSIs)作为一种抗生素的可能代替品,具有广阔的应用前景.一些研究指出QSIs与传统抗菌药物联合使用可以在提高药效的同时降低细菌耐药性.随着QSIs使用量地逐渐增大,在环境中可能与传统抗菌剂以混合的形式存在,因此有必要研究QSIs与传统抗菌剂的潜在联合毒性效应.但是,在目前的相关联合毒性效应研究中,被研究的传统抗菌剂种类有限,传统抗菌剂与QSIs的联合毒性效应可能由于传统抗菌剂的不同而发生改变.本文以大肠杆菌为受试生物,以磺胺和银类抗菌剂作为传统抗菌剂的代表,研究了两类传统抗菌剂与QSIs的二元以及三元联合毒性效应.结果表明,在磺胺-QSIs的30组二元联合毒性效应中,有24组表现为拮抗,6组表现为相加;在银类抗菌剂-QSIs的10组二元联合毒性效应中,有6组表现为拮抗,4组表现为相加;在磺胺-银类抗菌剂-QSIs的60组三元联合毒性效应中,有47组表现为拮抗,13组表现为相加.通过对比2种银类抗菌剂与QSIs的二元联合毒性效应,可以看出2种银类抗菌剂提供制毒部分的可能均为银离子;并且由于银类抗菌剂能最快地进入细菌细胞并完成与巯基的结合进而发挥药效,所以在三元混合中,银类抗菌剂可能起主要作用.
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  • [1] 苏建强, 黄福义, 朱永官. 环境抗生素抗性基因研究进展[J]. 生物多样性, 2013, 21(4):481-487.

    SU J Q, HUANG F Y, ZHU Y G. Advances in environmental antibiotic resistance genes[J]. Biodiversity, 2013, 21(4):481-487(in Chinese).

    [2] CHRISTOPHER, BONNIE W A, BASSLER. Quorum sensing:Cell-to-cell communication in bacteria[J]. Annu Rev Cell Dev Biol, 2005, 21:319-346.
    [3] RASMUSSEN T B, GIVSKOV M. Quorum-sensing inhibitors as anti-pathogenic drugs[J]. International Journal of Medical Microbiology, 2006, 296(2):149-161.
    [4] BRACKMAN G, COS P, MAES L, et al. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo[J]. Antimicrobial Agents & Chemotherapy, 2011, 55(6):2655-2661.
    [5] CHRISTENSEN L D, VAN GENNIP M, JAKOBSEN T H, et al. Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model[J]. The Journal of Antimicrobial Chemotherapy, 2012, 67(5):1198-1206.
    [6] HENTZER M, RIEDEL K, RASMUSSEN T B, et al. Inhibition of quorum sensing in pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound[J]. Microbiology, 2002, 148:87-102.
    [7] 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. Preliminary study on the combined toxicity of sulfa antibiotics and quorum sensing inhibitors to luminescent bacteria and its mechanism[J]. Environmental Chemistry, 2014, 33(12):2068-2075(in Chinese).

    [8] SLAWSON R M, LEE H, TREVORS J T. Bacterial interactions with silver[J]. Biology of Metal, 1990, 3(3):151-154.
    [9] 廖立新, 刘仔兰, 赵英, 等. 硝酸银软膏抗菌作用的研究[J]. 江西医学检验, 2001, (6):349-346. LIAO L X, LIU Z L, ZHAO Y, et al. Study on the antibacterial effect of silver nitrate ointment[J]. Jiangxi Medical Examination, 2001

    , 19(6):349-346(in Chinese).

    [10] OVINGTON. Nanocrystalline Silver:Where the old and familiar meets a new frontier[J]. Wounds, 2001, 13(2):5-10.
    [11] ADHYA A, BAIN J, RAY O, et al. Healing of burn wounds by topical treatment:A randomized controlled comparison between silver sulfadiazine and nano-crystalline silver[J]. Journal of Basic and Clinical Pharmacy, 2014, 6(1):29-34.
    [12] JOSE RUBEN M-R. Silver enhances antibiotic activity against gram-negative bacteria[J]. Science Translational Medicine, 2013, 190(5):190-211.
    [13] 郭春兰, 席祖洋, 戴德兰. 纳米银敷料结合抗生素用于慢性伤口感染干预效果的研究[J]. 中国医药导报, 2017, 14(28):60-64.

    GUO C L, XI Z Y, DAI D L. Study on the intervention effect of nano-silver dressing combined with antibiotics for chronic wound infection[J]. China Medical Journal, 2017, 14(28):60-64(in Chinese).

    [14] 吴秀琴. 抗生素联合纳米银抗菌水凝胶治疗慢性宫颈炎的临床应用[J]. 青海医药杂志, 2009, 39(12):34-35.

    WU X Q. Clinical application of antibiotics combined with silver nanoparticles in the treatment of chronic cervicitis[J]. Qinghai Medical Journal, 2009, 39(12):34-35(in Chinese).

    [15] BRODERIUS S J, KAHL M D, HOGLUND M D. Use of joint toxic response to define the primary mode of toxic action for diverse industrial organic chemicals[J]. Environmental Toxicology and Chemistry, 1995, 14(9):1591-1605.
    [16] WANG D, SHI J, XIONG Y, et al. A QSAR-based mechanistic study on the combined toxicity of antibiotics and quorum sensing inhibitors against Escherichia coli[J]. Journal of Hazardous Materials, 2018, 341:438-447.
    [17] 王志航, 冯雪, 李树仁, 等. 细菌群体感应通讯系统淬灭及应用[J]. 药物生物技术, 2018, 25(5):443-447.

    WANG Z H, FENG X, LI S R, et al. Quenching and application of bacterial quorum sensing communication system[J]. Pharmaceutical Biotechnology, 2018, 25(5):443-447(in Chinese).

    [18] WANG D, LIN Z, DING X, et al. The comparison of the combined toxicity between gram-negative and gram-positive bacteria:A case study of antibiotics and quorum-sensing inhibitors[J]. Molecular informatics, 2016, 35(2):54-61.
    [19] LONG X, WANG D, LIN Z, et al. The mixture toxicity of environmental contaminants containing sulfonamides and other antibiotics in Escherichia coli:Differences in both the special target proteins of individual chemicals and their effective combined concentration[J]. Chemosphere, 2016, 158:193-203.
    [20] CHEN C, WANG D, WANG H, et al. A SAR-based mechanistic study on the combined toxicities of sulfonamides and quorum sensing inhibitors on Escherichia coli[J]. SAR & QSAR in Environmental Research, 2017, 28(7):595-608.
    [21] LI W R, SUN T L, ZHOU S L, et al. A comparative analysis of antibacterial activity, dynamics, and effects of silver ions and silver nanoparticles against four bacterial strains[J]. International Biodeterioration & Biodegradation, 2017, 123:304-310.
    [22] VAZQUEZ-MUNOZ R, BORREGO B, JUAREZ-MORENO K, et al. Toxicity of silver nanoparticles in biological systems:Does the complexity of biological systems matter?[J]. Toxicology Letters, 2017, 276:11-20.
    [23] FUQUA W C, WINANS S C, GREENBERG E P. Quorum sensing in bacteria:The luxr-luxi family of cell density-responsive transcriptional regulators[J]. Journal of Bacteriology, 1994, 176(2):269-275.
    [24] R J D GALLOWAY W, T HODGKINSON J, BOWDEN S, et al. Quorum sensing in gram-negative bacteria:Small-molecule modulation of AHL and AI-2 quorum sensing pathways[J]. Chemical Reviews, 2011, 111(1):28-67.
    [25] RICHTER M K, FOCKS A, SIEGFRIED B, et al. Identification and dynamic modeling of biomarkers for bacterial uptake and effect of sulfonamide antimicrobials[J]. Environmental Pollution, 2013, 172:208-215.
    [26] LI H, GAO Y, LI C, et al. A comparative study of the antibacterial mechanisms of silver ion and silver nanoparticles by Fourier transform infrared spectroscopy[J]. Vibrational Spectroscopy, 2016, 85:112-121.
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  • 收稿日期:  2019-04-01

新型抗菌剂——群体感应抑制剂与传统抗菌剂对大肠杆菌的联合毒性效应

    通讯作者: 沈洪艳, E-mail: shy0405@sina.com
  • 1. 河北科技大学环境与工程学院, 石家庄, 050011;
  • 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:

国家自然科学基金(41373096,21577105,21777123),国家环保公益课题(201509041-05),河北省自然科学基金(B2014208068),河北省药用分子化学实验室开放基金,河北省环保厅公益课题,河北省重点学科建设基金,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(PCRRK16007),水体污染控制与治理科技重大专项(2018ZX07109-1),上海市科学技术委员会科研计划课题(17DZ1200103,14DZ2261100),环境化学与生态毒理学国家重点实验室开放基金课题(KF2016-11)和111工程资助.

摘要: 群体感应抑制剂(QSIs)作为一种抗生素的可能代替品,具有广阔的应用前景.一些研究指出QSIs与传统抗菌药物联合使用可以在提高药效的同时降低细菌耐药性.随着QSIs使用量地逐渐增大,在环境中可能与传统抗菌剂以混合的形式存在,因此有必要研究QSIs与传统抗菌剂的潜在联合毒性效应.但是,在目前的相关联合毒性效应研究中,被研究的传统抗菌剂种类有限,传统抗菌剂与QSIs的联合毒性效应可能由于传统抗菌剂的不同而发生改变.本文以大肠杆菌为受试生物,以磺胺和银类抗菌剂作为传统抗菌剂的代表,研究了两类传统抗菌剂与QSIs的二元以及三元联合毒性效应.结果表明,在磺胺-QSIs的30组二元联合毒性效应中,有24组表现为拮抗,6组表现为相加;在银类抗菌剂-QSIs的10组二元联合毒性效应中,有6组表现为拮抗,4组表现为相加;在磺胺-银类抗菌剂-QSIs的60组三元联合毒性效应中,有47组表现为拮抗,13组表现为相加.通过对比2种银类抗菌剂与QSIs的二元联合毒性效应,可以看出2种银类抗菌剂提供制毒部分的可能均为银离子;并且由于银类抗菌剂能最快地进入细菌细胞并完成与巯基的结合进而发挥药效,所以在三元混合中,银类抗菌剂可能起主要作用.

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