Integrative Microbial and Chemical Genomics to Decipher Antibiotic Resistance Mechanisms and Developing Innovative Antimicrobial Approaches

The emergence and global spread of antimicrobial resistance (AMR) pose one of the most critical threats to public health in the 21st century. While whole-genome sequencing has provided unprecedented insights into the genetic makeup of antimicrobial-resistant pathogens, there remains a pressing need to functionally annotate microbial genomes and systematically dissect the molecular pathways that drive AMR, persistence, and susceptibility to antimicrobials. Simultaneously, advances in chemical genomics and high-throughput screening technologies have opened new avenues for discovering small adjuvant molecules or combinations that modulate microbial fitness and virulence.

This Research Topic aims to bring together novel research that integrates microbial genomics, chemical genomics, and systems biology to advance our understanding of antimicrobial action and AMR.
We seek to highlight interdisciplinary approaches that leverage high-throughput functional genomics—such as CRISPR interference (CRISPRi) screening, transposon sequencing (Tn-Seq), CRISPRi-TnSeq, RNA-Seq, metabolomics, and phenotypic profiling—in combination with chemical perturbation to explore microbial physiology at scale.

We welcome contributions that explore both fundamental questions about microbial gene function and applied goals such as identifying new targets, antimicrobial compounds, adjuvant molecules or combinations, revealing drug–gene interactions, mapping resistance networks, and predicting therapeutic vulnerabilities.

We encourage the submission of Original Research, Mini-Reviews, Reviews, Perspectives, and Methods articles focusing on, but not limited to, the following sub-themes:

• Genome-wide functional screening in bacteria using CRISPRi, Tn-Seq, barcoded mutant libraries, or
combinatorial genomics approaches under antimicrobial stress.

• Chemical-genomic profiling to identify drug targets, AMR determinants, and synthetic lethal interactions.

• Multi-omics integration (genomics, transcriptomics, metabolomics, proteomics) for mechanistic dissection of
antimicrobial activity and adaptation, as well as AMR evolution.

• Systems-level modeling of microbial networks and drug-response dynamics.

• Discovery and characterization of novel small adjuvant molecules or combinations or natural products with
antimicrobial or anti-virulence activities.

• Evolutionary and adaptive responses to chemical perturbations in microbial populations.

• Microbiome-wide chemical-genomic studies and their implications for host-pathogen interactions and drug
efficacy.

This Research Topic will provide a platform for cutting-edge research at the interface of microbial functional genomics and chemical biology. By fostering a systems-level view of microbial responses to chemical stress, we aim to uncover vulnerabilities that can be exploited for therapeutic development and to better understand the genetic underpinnings of resistance. Contributions will help drive innovation in antimicrobial discovery and contribute to global efforts to combat AMR.

Please note that Systems Microbiology does not consider descriptive studies that are solely based on amplicon (e.g., 16S rRNA) profiles, unless they are accompanied by a clear hypothesis and experimentation, and provide insight into the microbiological system or process being studied.

Article types and fees

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

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

Keywords: Chemical genomics, Functional genomics, Antimicrobial resistance, CRISPRi screening, Microbial systems biology, Drug–gene interactions

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.