The DOI matches its Crossref record; 126 of the 126 references it cites were found in a registry or an index.
Systems-level antimicrobial drug and drug synergy discovery
Abstract
Here, we review the 'target-centric' genomic strategy to antimicrobial discovery and share our perspective on identification, validation and prioritization of potential antimicrobial drug targets in the context of emerging chemical biology, genomics and phenotypic screening strategies. We propose that coupling the dual processes of antimicrobial small-molecule screening and target identification in a whole-cell context is essential to empirically annotate 'druggable' targets and advance early stage antimicrobial discovery. We also advocate a systems-level approach to annotating synthetic-lethal genetic interactions comprehensively within yeast and bacteria models. The resulting genetic interaction networks provide a landscape to rationally predict and exploit drug synergy between cognate inhibitors. We posit that synergistic combination agents provide an important and largely unexploited strategy to 'repurpose' existing chemical space and simultaneously address issues of potency, spectrum, toxicity and drug resistance in early stages of antimicrobial drug discovery.
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“Synthetic lethal interactions are of particular interest as they can be harnessed to identify new antibiotic or cancer therapeutic targets (6, 7).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [6]
Citations
Cites
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Self-citation
Cited by
Sorted by citations
The re-emergence of natural products for drug discovery in the genomics era
Harvey, A. L., Edrada‐Ebel, R., & Quinn, R. J. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4510 · Cited by 2,654
A global genetic interaction network maps a wiring diagram of cellular function
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Self-citationTarget identification and mechanism of action in chemical biology and drug discovery
Schenone, M., Dančík, V., Wagner, B. K., & Clemons, P. A. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1199 · Cited by 1,147
Drug combinations: a strategy to extend the life of antibiotics in the 21st century
Tyers, M., & Wright, G. D. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0141-x · Cited by 849
Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801
Metadata
- Authors
- Roemer, T., & Boone, C.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- University of Toronto (CA)
- Corresponding author
- Roemer, Terry
- Boone, Charles
- ORCID
- Boone, Charles
- Venue
- Nature Chemical Biology
- Published
- 2013-03-18
- Volume
- 9
- Issue
- 4
- Pages
- 222-231
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2085719025
- Semantic Scholar
- a4baefb4f35813be6ec8cc6c076833402fcc8f24
- Cited by
- 159
- References
- 126
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 13 · 2021: 8 · 2020: 15 · 2019: 9 · 2018: 10 · 2017: 18 · 2016: 19 · 2015: 19 · 2014: 16 · 2013: 7
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP-57830)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- antimicrobial drug discovery, drug synergy, synthetic lethality, genetic interaction networks, drug resistance, yeast model, druggable targets
- MeSH terms
- Anti-Bacterial Agents, Antifungal Agents, Bacteria, Drug Synergism, Genotype, Humans, Phenotype, Yeasts, Genomics, Small Molecule Libraries, Validation Studies as Topic, Drug Discovery, High-Throughput Screening Assays, Molecular Targeted Therapy
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