Targets and Strategies to Address Antimicrobial Resistance

Antimicrobial resistance (AMR) is an escalating global health threat that jeopardizes the effectiveness of existing antibiotics and antimicrobial agents. While strategies like drug repurposing and combination therapies offer temporary solutions, the urgent need for new chemical entities with novel mechanisms of action remains unmet. Advances in understanding microbial resistance mechanisms, persistence, and essential biological processes, together with breakthroughs in chemical biology, are opening new pathways to identify and exploit vulnerabilities in pathogens. Chemical biology approaches — including chemical probes, activity-based profiling, and chemoproteomics — are reshaping how we discover and validate antimicrobial targets, offering unprecedented insights into pathogen physiology and drug interactions. Integrating synthetic chemistry, target identification, and mechanistic understanding is critical to developing next-generation antimicrobials capable of bypassing or overcoming resistance pathways.

This Research Topic aims to highlight cutting-edge strategies addressing AMR through the combined power of chemical innovation, novel biological targets, and advanced target identification approaches. We solicit contributions presenting new small molecules, synthetic derivatives, or natural products with antimicrobial activity, as well as research uncovering and validating microbial targets essential to pathogen survival or virulence.

Special emphasis will be placed on how chemical biology propels antibiotic discovery — from identifying previously untargeted enzymes, pathways, or processes using activity-based probes or small-molecule screens, to mapping resistance mechanisms like enzyme inactivation, efflux pumps, or target modifications. We welcome studies on designing and optimizing small molecules through high-throughput screening, fragment-based approaches, or structure-guided design; probing bacterial physiology using biosensors, fluorescent tagging, or chemoproteomics; and combining synthetic biology with chemical biology to unlock cryptic biosynthetic pathways for novel natural products.

Our goal is to showcase how interdisciplinary approaches that blend synthetic chemistry, chemical biology, and advanced biological techniques can overcome the hurdles of resistance and deliver next-generation antimicrobials. This collection will serve as a foundation for innovative antimicrobial strategies ready to combat resistant pathogens.

We welcome original research articles, brief reports, reviews, mini reviews and perspectives on topics including, but not limited to:

• Discovery and synthesis of new antimicrobial agents
• Identification and validation of novel bacterial or fungal targets
• Mechanisms of resistance and chemical strategies to overcome them
• Chemical biology tools (e.g., chemical probes, activity-based profiling, inhibitors) for studying microbial pathways
• Advances in target identification technologies (e.g., proteomics, chemoproteomics, biosensors)
• Case studies integrating synthetic chemistry and biological evaluation

Researchers from medicinal chemistry, bioorganic chemistry, chemical biology, microbiology, synthetic biology, and related fields are encouraged to contribute.

Article types and fees

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

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... 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:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review

Keywords: antimicrobial resistance, medicinal chemistry, bioorganic chemistry, chemical biology, target identification, new antibiotics, resistance mechanisms

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.