群体感应抑制剂与磺胺甲恶唑、盐酸强力霉素对大肠杆菌的联合毒性及其机制初探

群体感应抑制剂(QSIs)具有不产生抗药性的特点，从而被作为抗生素的可能替代品，具有广阔的应用前景，因此其存在着与传统抗生素环境联合暴露的可能，但是目前尚缺乏相关联合效应的研究。本文以大肠杆菌(Escherichia coli)为受试生物，测定了7种QSIs(DL-焦谷氨酸、N-乙烯基吡咯烷酮、呋喃酮乙酸酯、2-甲基四氢呋喃-3-酮、3,4-二溴-2(5H)-呋喃酮、(R)-3-吡咯烷醇、D-脯氨醇)分别与磺胺甲恶唑(SMX)和盐酸强力霉素(DH)的二元联合毒性，并初步探讨了它们的联合作用机制。结果表明，前5种QSIs作用于AI-2类信号分子介导的群体感应系统，与AI-2类信号分子竞争结合LsrB蛋白，此通路与SMX、DH的作用通路互不影响，因此联合效应为相加；后2种QSIs作用于AI-1类信号分子介导的群体感应系统，与AI-1类信号分子竞争结合SdiA蛋白，而SMX、DH的作用可能刺激SdiA蛋白的表达，从而需要消耗更多的QSIs与SdiA结合，因而联合效应为拮抗。本实验研究可为传统抗生素与QSIs联合暴露的生态风险评价提供一定理论基础。

Joint Effects and Mechanism of Binary Toxicity of Quorum Sensing Inhibitors with Sulfamethoxazole and Doxycycline Hyclate to Escherichia coli

Quorum sensing inhibitors (QSIs) are recognized as a promising alternative to the antibiotics, due to their outstanding characteristics of not inducing drug resistance. Therefore, there stands a high possibility that the environmental organisms are exposed simultaneously to QSIs and antibiotics. However, litter research has been conducted on their potential joint effects on the organisms so far. In this study, seven potential QSIs, i.e., DL-pyroglutamic acid, N-vinyl-2-pyrrolidone, furaneol acetate, 2-methyltetrahy-drofuran -3-one, 3,4-dibromo-5H-furan-2-one, (R)-3-hydroxypyrrolidine, D(-)Prolinol), and two types of antibiotics, i.e., sulfamethoxazole (SMX) and tetracycline (DH), were investigated for their binary mixture toxicity on Escherichia coli (E.coli), and the possible mechanism was explored as well. The results revealed that the first five QSIs acts on the AI-2-mediated QS system through binding competitively to LsrB proteins, which exerted no influence on the pathways of SMX and DH and thus presented simply additive joint effects with the antibiotics. Whereas, the latter two QSIs primarily targeted the AI-1-mediated QS system by binding to SdiA proteins. Since SMX and DH may stimulate the production of SdiA protein, which consumed more QSI molecules, the joint effects of the second kind of QSIs with SMX and DH were antagonism. This study provides some basic data for ecological risk assessment on the joint effect of the QSIs and traditional antibiotics.