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    首頁» 科研進展» 雷曉光課題組在闡明“超級細菌”耐藥機制和開發潛在新一代抗生素研究中取得進展

    雷曉光課題組在闡明“超級細菌”耐藥機制和開發潛在新一代抗生素研究中取得進展

     

    多重耐藥細菌,特別是超級細菌的出現及蔓延已成為威脅人類健康的全球性問題。闡明新的耐藥機制和開發克服耐藥性的新一代抗生素是當前學術界和制藥工業界共同的迫切需求銅綠假單胞菌(Pseudomonas aeruginosa)是醫院內常見的感染病原菌,在免疫功能低下的病人中可導致高發病率和死亡率,世界衛生組織早已將其列為“critical priority pathogens”。銅綠假單胞菌是一種革蘭氏陰性菌,其外膜通透性很低,能夠有效阻礙藥物分子進入到細胞內,對許多臨床重要的抗生素(如氨芐西林、阿莫西林和萬古霉素等)具有天然耐受性,因此是一類名副其實的超級細菌

     

    近日,雷曉光課題組在《Chemical Science》期刊上發表了題為“De novo synthesis, structural assignment and biological evaluation of pseudopaline, a metallophore produced by Pseudomonas aeruginosa的研究論文,首次通過化學全合成以及天然產物分離獲得了一類對于促進銅綠假單胞菌生長和耐藥至關重要的天然產物分子pseudopaline,并且確定了pseudopaline相對和絕對立體構型。在此基礎之上,雷曉光課題組初步探索了pseudopaline的生物活性,證明該分子是一類廣譜的金屬離子螯合劑,可以促進銅綠假單胞菌對二價金屬離子的轉運、吸收,從而促進該細菌生長和產生耐藥性。最后,雷曉光課題組還合成了pseudopaline-熒光素的偶聯體,證明了該偶聯體可以被有效地轉運進入銅綠假單胞菌,從而驗證了利用該天然產物開發新一代抗生素、例如新型“特洛伊木馬”類型的pseudopaline-抗生素偶聯體,幫助克服耐藥機制的可行性。

     

    雷曉光課題組的博士生張健和博士后趙天湖博士、楊榮文博士為該論文的共同第一作者,雷曉光教授為通訊作者,瑞士羅氏制藥公司創新藥物研發主管沈宏博士為該研究工作提供了幫助。該工作得到國家自然科學基金(杰出青年基金、重點項目和創新群體項目)、科技部重點研發計劃、973項目、北大-清華生命聯合中心、以及瑞士羅氏制藥公司早期創新藥物研發項目的資助。楊榮文博士還得到了北大-清華生命聯合中心優秀博士后計劃的資助。目前雷曉光課題組正在與瑞士羅氏制藥工作合作,積極推進后期新一代抗生素藥物的開發。

     20190625156145005367006344.jpg

    原文鏈接: https://pubs.rsc.org/en/content/articlepdf/2019/SC/C9SC01405E

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