Bacterial secondary metabolites represent a vast arsenal of bioactive compounds with the potential to combat antimicrobial resistance (AMR). Environmental microbes, particularly from extreme and underexplored habitats, produce diverse metabolites that can serve as novel antibiotics. Advanced genome mining and synthetic biology approaches are now unlocking previously silent biosynthetic gene clusters (BGCs), enabling the discovery of next-generation antimicrobials.

One promising strategy in AMR combat is targeting bacterial persisters-dormant cells that evade antibiotics and contribute to chronic infections. Metabolite-based therapeutics, capable of either reactivating persisters or exploiting their metabolic vulnerabilities, offer a novel approach to eliminating these resilient bacterial populations. Similarly, repurposing bacterial metabolites, such as ionophores and antivirulence compounds, provides a sustainable alternative to traditional antibiotics. These metabolites, when used in synergy with existing drugs, enhance antimicrobial efficacy while minimizing resistance evolution.

Synthetic biology and metabolic engineering further enhance the potential of bacterial metabolites by optimizing their production, activity, and pharmacokinetics. Engineered microbial hosts enable the scalable biosynthesis of rare or modified metabolites, improving their therapeutic viability. Advances in AI-driven drug discovery and fermentation technology are accelerating the translation of soil-derived metabolites into clinically approved therapies.

By integrating genome mining, metabolic engineering, and rational drug design, bacterial metabolites offer a sustainable and innovative solution to the global AMR crisis. Harnessing these natural products effectively could lead to the next generation of antimicrobial therapies, bridging the gap between environmental discovery and clinical application.

In this article collection we invite contributions that include, but are not limited to, the following sub-topics:

o The discovery and characterization of new antimicrobial bacterial metabolites.

o Strategies for combating bacterial persister cells through metabolite exploitation.

o The role of synthetic biology in optimizing metabolite production and function.

o Translational research bridging environmental discovery to clinical application.

o AI-driven drug discovery and fermentation technology for accelerating the translation of soil-derived
metabolites into clinically approved therapies.

In this Research Topic we consider the following article types: Methods, Mini Review, Original Research, Review.

Are you interested in contributing a manuscript to this Research Topic?

Bacterial Metabolites: Redefining Strategies to Combat Antimicrobial Resistance