Bacterial Metabolites: Redefining Strategies to Combat Antimicrobial Resistance

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.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Bacterial Metabolites, Antimicrobial Resistance, Genome Mining, Persister Cells, Synthetic Biology

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.