香港大学化学系孙红哲研究团队报道了基于金属的对抗抗菌素耐药性的方法。2025年3月10日，国际知名学术期刊《美国化学会杂志》发表了这一成果。

从这个角度来看，该课题组强调了过去10年在发展金属基战略以克服抗生素耐药性危机方面的重要示范研究。具体来说，该课题组研究人员根据其作用方式将这些金属抗菌剂分为五类（即，金属酶和金属结合酶抑制剂，膜干扰剂，摄取/外排系统抑制剂/调节剂，持续抑制剂和氧化应激诱导剂）。与传统抗生素相比，金属抗菌剂的显著优势在于其多靶点机制，从而降低了产生耐药性的可能性。

然而，该课题组注意到金属抗菌剂的这种作用方式也可能引起人们对其潜在副作用的担忧，因为它们对病原体和宿主的选择性较低，这似乎是下游转化研究的最大障碍。课题组预计，通过重新利用（金属）药物与抗生素以及通过配方优化其吸收途径以实现靶向递送的联合治疗将是对抗AMR的有力方法。尽管面临重大挑战，金属抗微生物药物仍为耐药细菌感染的治疗干预提供了巨大的机会。

据了解，抗微生物药物耐药性（AMR）细菌的迅速紧急和传播以及缺乏正在开发的新抗生素对全球卫生保健系统构成严重威胁。因此，开发更有效的治疗方法来克服AMR是非常可取的。金属离子作为抗菌剂有着悠久的历史，金属基化合物由于其独特的作用机制，在抗抗生素耐药性方面引起了科学界的更多兴趣。此外，它们还可以作为抗生素佐剂，以提高临床主题抗生素的疗效。

附：英文原文

Title: Metal-Based Approaches for the Fight against Antimicrobial Resistance: Mechanisms, Opportunities, and Challenges

Author: Chenyuan Wang, Xueying Wei, Liang Zhong, Chun-Lung Chan, Hongyan Li, Hongzhe Sun

Issue&Volume: March 10, 2025

Abstract: The rapid emergency and spread of antimicrobial-resistant (AMR) bacteria and the lack of new antibiotics being developed pose serious threats to the global healthcare system. Therefore, the development of more effective therapies to overcome AMR is highly desirable. Metal ions have a long history of serving as antimicrobial agents, and metal-based compounds are now attracting more interest from scientific communities in the fight against AMR owing to their unique mechanism. Moreover, they may also serve as antibiotic adjuvants to enhance the efficacy of clinically used antibiotics. In this perspective, we highlight important showcase studies in the last 10 years on the development of metal-based strategies to overcome the AMR crisis. Specifically, we categorize these metallo-antimicrobials into five classes based on their modes of action (i.e., metallo-enzymes and metal-binding enzyme inhibitors, membrane perturbants, uptake/efflux system inhibitors/regulators, persisters inhibitors, and oxidative stress inducers). The significant advantages of metallo-antimicrobials over traditional antibiotics lie in their multitargeted mechanisms, which render less likelihood to generate resistance. However, we notice that such modes of action of metallo-antimicrobials may also raise concern over their potential side effects owing to the low selectivity toward pathogens and host, which appears to be the biggest obstacle for downstream translational research. We anticipate that combination therapy through repurposing (metallo)drugs with antibiotics and the optimization of their absorption route through formulation to achieve a target-oriented delivery will be a powerful way to combat AMR. Despite significant challenges, metallo-antimicrobials hold great opportunities for the therapeutic intervention of infection by resistant bacteria.

DOI: 10.1021/jacs.4c16035

Source: https://pubs.acs.org/doi/full/10.1021/jacs.4c16035