Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Saarland University Department of Pharmacy, Saarbrücken, Germany.
German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany.
Microb Biotechnol. 2024 Nov;17(11):e70032. doi: 10.1111/1751-7915.70032.
Natural products have proven themselves as a valuable resource for antibiotics. However, in view of increasing antimicrobial resistance, there is an urgent need for new, structurally diverse agents that have the potential to overcome resistance and treat Gram-negative pathogens in particular. Historically, the search for new antibiotics was strongly focussed on the very successful Actinobacteria. On the other hand, other producer strains have been under-sampled and their potential for the production of bioactive natural products has been underestimated. In this mini-review, we highlight prominent examples of novel anti-Gram negative natural products produced by Gram-negative bacteria that are currently in lead optimisation or preclinical development. Furthermore, we will provide insights into the considerations and strategies behind the discovery of these agents and their putative applications.
天然产物已被证明是抗生素的宝贵资源。然而，鉴于抗菌药物耐药性不断增加，迫切需要具有克服耐药性潜力并能特别治疗革兰氏阴性病原体的新型、结构多样的药物。从历史上看，新型抗生素的寻找主要集中在非常成功的放线菌上。另一方面，其他生产菌株的采样不足，其产生生物活性天然产物的潜力被低估。在这个小型综述中，我们强调了目前处于优化先导化合物或临床前开发阶段的由革兰氏阴性细菌产生的新型抗革兰氏阴性天然产物的突出实例。此外，我们还将深入探讨发现这些药物的考虑因素和策略及其潜在应用。
