纳米抗菌材料对细菌耐药性进化的影响

With the increasing production and application of antibacterial nanomaterials in consumer products and biomedical areas, their concentrations in the environment increase gradually and the potential ecological impacts and health risk have received much attention. It’s well known that traditional antibacterial products (e.g., disinfection and antimicrobial agents) can induce resistant evolution in bacteria and accelerate the transport of antibacterial resistance genes. The physicochemical properties and antibacterial mechanisms of nanomaterials are significantly different from that of traditional antibacterial agents. Will they also induce resistant evolution in bacteria? Are there structure-effect relationships between nanomaterial properties and the induced effect? But to date, there are sporadic studies in this area and the intrinsic adaptive and evolution mechanisms are still unidentified. In this study we’ll focus on the mechanism of resistant evolution in bacteria under long-term and low-dose exposure to antibacterial nanomaterials. The effects of nanomaterial on bacterial evolution, horizontal gene transfer within and across genera, and the changes of structure and function of microbial community will be systemically explored. The structural effects of nanomaterial will be discussed. Different levels of indicators, e.g., from susceptibility to stability, will be utilized to assess the inducing effects. The outcome of this study is a prerequisite for the application of antibacterial nanomaterials, and is also the theoretical basis for scientific evaluation of their health risk and ecological impacts. Additionally, the results may also provide technical support for the design of environmental friendly, targeted, efficient antibacterial nanomaterial.

随着纳米抗菌材料在日用品、生物医药等领域使用范围日益扩大，环境浓度也逐渐增大，其潜在的生态效应及健康风险受到关注。常用抗菌剂（如消毒抑菌产品）可诱导细菌耐药性、加速耐药基因的传播，纳米抗菌材料在理化性质、杀菌机理上与传统抗菌剂、抗生素有显著不同之处，是否也可显著改变细菌耐药性？在诱导细菌进化方面是否存在构效关系？但相关研究尚不多见，纳米抗菌材料胁迫下细菌内在适应性、耐药性进化的分子机制亦不明确。本项目拟研究常见纳米抗菌材料长期低剂量暴露诱导细菌耐药性进化的分子机制，系统探讨不同物理化学特性的纳米颗粒对单菌进化、抗性基因菌间传播、菌群结构功能耐药性改变的影响，建立从灵敏性到稳定性的多指标、多层次评价体系。本研究是纳米抗菌材料推广应用的前提，是科学评价纳米颗粒健康风险及生态效应的理论基础，也为设计环境友好、有针对性、高效的纳米抗菌材料提供技术支撑。

抗生素暴露诱导细菌耐药性已成为世界范围内的重大公共卫生安全问题。纳米抗菌剂由于其独特多样的理化性质、多重杀菌机制被认为是对抗耐药菌的有利武器。作为有巨大应用前景的纳米抗菌剂是否也会导致细菌耐药性进化？会不会增加细菌致病性导致生物安全性风险？如何利用纳米技术改变细菌不利进化？关于这方面的研究非常缺乏。特别是环境暴露下细菌的耐药、致病性进化具有暴露时间长、剂量低，细菌进化隐蔽、缓慢、复杂，细菌形成耐药机制不清等特点、难点。. 本项目围绕新型纳米抗菌剂环境暴露—细菌适应性进化—衍生致病性耐药性开展系统研究，一方面发现了细菌针对纳米抗菌剂独特的（区别于传统抗生素）压力应答机制，发现新抑菌靶点、机制提高杀菌效率，并避免衍生细菌耐药性。另一方面，阐释了长期、低剂量纳米抗菌剂暴露下细菌调控网络的适应性进化，与耐受性、耐药性、致病性进化的共通与差异，评估纳米抗菌剂长期生态安全性。这些研究为设计环境友好的纳米抗菌材料、对抗多重耐药菌、遏制细菌耐药性进化提供可应用的研究基础，对准确评估抗菌纳米颗粒生物安全性具有重要意义。. 项目执行期内共发表SCI期刊论文13篇（第一或第二标注），含Environ Sci Technol （4篇），Water Res，Nano Lett，Nano Today等；培养硕士研究生10名、博士研究生2名。相关研究获得第九届环境化学大会优秀展报奖、第十届全国环境大会优秀报告奖，被评选为Environmental Science: Nano 当期的热点文章。项目主持人2021年获得国家杰出青年科学基金资助项目，2021年推荐为Frontiers in Microbiology、Frontiers in Bioengineering and Biotechnology、Frontiers in Environmental Science期刊审稿编辑。