ArticleEBioMedicine2024
High-throughput screening of small-molecules libraries identified antibacterials against clinically relevant multidrug-resistant A. baumannii and K. pneumoniae.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A bibliometric analysis and systematic review of drug repurposing against drug-resistant ESKAPE pathogens: a particular focus onFrontiers in microbiology · 2025Pooled it
- Antibacterial mechanism and in vivo efficacy of cladribine against carbapenem-resistant Klebsiella pneumoniae.BMC microbiology · 2026Article
- Reprogrammed SimCells for antimicrobial therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- High-Throughput Screening of FDA-Approved Drugs for Antibacterial and Antibiofilm Activities Against Multidrug-resistantACS omega · 2026Article
- ENOblock synergizes with colistin to treat Acinetobacter baumannii infections.EMBO molecular medicine · 2025Article
- Measurement and prediction of small molecule retention by Gram-negative bacteria based on a large-scale LC/MS screen.Scientific reports · 2025Article
- In Silico Approach for Antibacterial Discovery: PTML Modeling of Virtual Multi-Strain Inhibitors AgainstPharmaceuticals (Basel, Switzerland) · 2025Article
- Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps.Antimicrobial agents and chemotherapy · 2024Review
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
backgroundThe current pipeline for new antibiotics fails to fully address the significant threat posed by drug-resistant Gram-negative bacteria that have been identified by the World Health Organization (WHO) as a global health priority. New antibacterials acting through novel mechanisms of action are urgently needed. We aimed to identify new chemical entities (NCEs) with activity against Klebsiella pneumoniae and Acinetobacter baumannii that could be developed into a new treatment for drug-resistant infections.
methodsWe developed a high-throughput phenotypic screen and selection cascade for generation of hit compounds active against multidrug-resistant (MDR) strains of K. pneumoniae and A. baumannii. We screened compound libraries selected from the proprietary collections of three pharmaceutical companies that had exited antibacterial drug discovery but continued to accumulate new compounds to their collection. Compounds from two out of three libraries were selected using "eNTRy rules" criteria associated with increased likelihood of intracellular accumulation in Escherichia coli.
findingsWe identified 72 compounds with confirmed activity against K. pneumoniae and/or drug-resistant A. baumannii. Two new chemical series with activity against XDR A. baumannii were identified meeting our criteria of potency (EC
interpretationThis work provides proof of principle for the screening strategy developed to identify NCEs with antibacterial activity against multidrug-resistant critical priority pathogens such as K. pneumoniae and A. baumannii. The screening and hit selection cascade established here provide an excellent foundation for further screening of new compound libraries to identify high quality starting points for new antibacterial lead generation projects.
fundingBMBF and GARDP.
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