Ahmad Mehrose, Aduru Sai Varun, Smith Robert P, Zhao Zirui, Lopatkin Allison J
Weill Cornell Medical College, Cornell University, New York, NY, USA.
Department of Chemical Engineering, University of Rochester, Rochester, NY, USA.
Nat Rev Microbiol. 2025 Feb 20. doi: 10.1038/s41579-025-01155-0.
The relationship between bacterial metabolism and antibiotic treatment is complex. On the one hand, antibiotics leverage cell metabolism to function. On the other hand, increasing research has highlighted that the metabolic state of the cell also impacts all aspects of antibiotic biology, from drug efficacy to the evolution of antimicrobial resistance (AMR). Given that AMR is a growing threat to the current global antibiotic arsenal and ability to treat infectious diseases, understanding these relationships is key to improving both public and human health. However, quantifying the contribution of metabolism to antibiotic activity and subsequent bacterial evolution has often proven challenging. In this Review, we discuss the complex and often bidirectional relationships between metabolism and the various facets of antibiotic treatment and response. We first summarize how antibiotics leverage metabolism for their function. We then focus on the converse of this relationship by specifically delineating the unique contribution of metabolism to three distinct but related arms of antibiotic biology: antibiotic efficacy, AMR evolution and AMR mechanisms. Finally, we note the relevance of metabolism in clinical contexts and explore the future of metabolic-based strategies for personalized antimicrobial therapies. A deeper understanding of these connections is crucial for the broader scientific community to address the growing crisis of AMR and develop future effective therapeutics.
细菌代谢与抗生素治疗之间的关系错综复杂。一方面，抗生素利用细胞代谢发挥作用。另一方面，越来越多的研究表明，细胞的代谢状态也会影响抗生素生物学的各个方面，从药物疗效到抗菌耐药性（AMR）的演变。鉴于AMR对当前全球抗生素储备和治疗传染病的能力构成日益严重的威胁，了解这些关系是改善公众健康和人类健康的关键。然而，量化代谢对抗生素活性及后续细菌进化的贡献往往颇具挑战。在本综述中，我们将探讨代谢与抗生素治疗及反应的各个方面之间复杂且通常是双向的关系。我们首先总结抗生素如何利用代谢来发挥其功能。然后，我们将通过具体阐述代谢对抗生素生物学三个不同但相关方面的独特贡献，即抗生素疗效、AMR进化和AMR机制，来关注这种关系的反方向。最后，我们指出代谢在临床环境中的相关性，并探索基于代谢的个性化抗菌治疗策略的未来。深入理解这些联系对于更广泛的科学界应对日益严重的AMR危机和开发未来有效的治疗方法至关重要。
