湖南大学化学化工学院冯欣欣课题组是一个跨学科的科研团队，拥有有机化学、药物化学、化学生物学、微生物学、分析化学背景的导师及研究生，并与国内外微生物、药物化学领域的顶尖课题组保持紧密合作。目前，我们的研究方向主要为具有抵抗细菌耐药性特性（即“抗-耐药性”）的抗菌药物的化学生物学研究。

课题简介及近期成果

耐药性细菌感染是严重影响人类生命健康及社会经济发展的重大问题。世界抗菌药物开发的困境主要源于传统抗生素固有的靶向机制，即其单一性地靶向细菌外膜以内的生物大分子靶点（如关键蛋白）而带来生长抑制性机制。传统抗生素的靶点选择使得细菌易于产生三种常见的耐药性：外膜对抗生素的阻挡作用形成“屏障性耐药”；蛋白靶点的易突变性促使细菌在药物压力下进化产生“进化性耐药”；细菌入侵细胞、以生长静止的休眠菌形式逃逸抗生素攻击的“藏匿性耐药”。由此可见，新一代抗菌药物的开发并非简单的分子结构改造问题，而是从根源上寻找具有“抗-耐药性”的抗菌靶点的关键科学问题。

在过去的几年中，以“多重生物分子靶向”策略为基础，课题组开发了一系列新型抗菌分子为克服上述耐药性问题提供思路。为了解决革兰氏阴性细菌的渗透性屏障问题，我们研究了外膜增敏佐剂与抗生素之间的协同作用，并提出了“衍生化增敏”策略，为抗生素增敏提供了一种通用方法（2022 ACSCB1，2023 JACS2，2024 Sci China-Chem3）。为了抑制进化性耐药，我们设计了多靶标抗菌药物并研究了它们的抗耐药机制。这些分子具有新颖的抗菌作用模式，例如膜-蛋白双重靶向（2014 JACS4，2014 JMC5，2015 PNAS6）、膜-DNA双重靶向（2021 Sci Adv7，2024 Sci Adv8，2021 Biomaterials9，2022 Chem Mater10，2022 Adv Healthc Mater11）、破坏细菌亚细胞结构空间有序度（2024 JACS12，受邀主封面），以及细菌内源活性氧风暴（PNAS审稿中）。这些分子有效根除细菌并抑制细菌进化性耐药。最后，我们通过细胞内体融合的方式，实现了双靶向寡聚物与胞内病原菌的精准亚细胞共定位，有效清除了胞内的持留性细菌（2023 JACS13，2022 CCSChem14）。

联系方式：xinxin_feng@hnu.edu.cn（邮箱）

2025.3-今 湖南大学化学生物学与纳米医学研究所，化学生物传感与计量学国家重点实验室，湖南大学化学化工学院，教授

2017.8-2025.3 湖南大学化学生物学与纳米医学研究所，化学生物传感与计量学国家重点实验室，湖南大学化学化工学院，副教授

2014.5-2017.8 GlucoSentient, Inc.，研发科学家

2014.5-2016.8 美国伊利诺伊大学（香槟校区）化学系，博士后(导师：Prof. Eric Oldfield)

2011.1-2014.5 美国伊利诺伊大学（香槟校区）化学系(导师：Prof. Eric Oldfield)

2009.8-2010.12 美国伊利诺伊大学（香槟校区）化学系(导师：Prof. Roman Boulatov)

2005.9-2009.6 南京大学化学系，本科

[1]（主持）目前承担国家自然科学基金面上项目一项，项目名称为《同时靶向菌膜与DNA的抗菌肽模拟物分子设计及其靶向杀灭胞内持留菌的机制研究》，项目批准号：22177031（60万元，2022.01-2025.12）。

[2]（主持）2021年结题一项国家自然科学基金青年科学基金项目，该项目名称为“基于靶点活性的双重原位抗分支杆菌素高通量筛选平台的建立以及分支杆菌DPPS抑制剂的筛选和优化研究”（21807031，2019.01-2021.12）。

[3]（主持）湖南省优秀青年基金获得者，“抗菌药物化学生物学”，20万元。

[4]（主持）湖南省湖湘青年英才获得者，30万元。

[5]（主持）国家重点研发计划湖南大学子课题，140万元（项目共2000万元）。

[6]（主持）抗菌符合涂层开发（横向课题），160万元。

[7]（主持）湖南省面上课题，5万元。

[8]（参与）长沙市科技计划项目——长沙市精准即时诊断（POCT）工程技术研究中心，12万元。

[9]（参与）功能有机小分子化学合成及表征，30万元。

[10]（参与）食品微生物性污染的快速超灵敏可视化检测新方法研究及设备开发，50万元。

[11]（参与）“千人 计划”顶尖人才与创新团队（Chad A. Mirkin），项目共3000万元。

[12]（参与）生物大分子化学生物学湖南省重点实验室，项目共100万元。

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