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| DOI | Resolve DOI: https://doi.org/10.1038/s41467-023-37624-4 |
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| Author | Search for: Liu, Dennis Y.ORCID identifier: https://orcid.org/0000-0002-0820-4345; Search for: Phillips, Laura; Search for: Wilson, Darryl M.; Search for: Fulton, Kelly M.1; Search for: Twine, Susan M.1; Search for: Wong, Alex; Search for: Linington, Roger G.ORCID identifier: https://orcid.org/0000-0003-1818-4971 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Funder | Search for: Natural Sciences and Engineering Research Council of Canada; Search for: National Research Council Canada |
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| Format | Text, Article |
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| Abstract | The rapid emergence of antimicrobial resistance presents serious health challenges to the management of infectious diseases, a problem that is further exacerbated by slowing rates of antimicrobial drug discovery in recent years. The phenomenon of collateral sensitivity (CS), whereby resistance to one drug is accompanied by increased sensitivity to another, provides new opportunities to address both these challenges. Here, we present a high-throughput screening platform termed Collateral Sensitivity Profiling (CSP) to map the difference in bioactivity of large chemical libraries across 29 drug-resistant strains of E. coli. CSP screening of 80 commercial antimicrobials demonstrated multiple CS interactions. Further screening of a 6195-member natural product library revealed extensive CS relationships in nature. In particular, we report the isolation of known and new analogues of borrelidin A with potent CS activities against cephalosporin-resistant strains. Co-dosing ceftazidime with borrelidin A slows broader cephalosporin resistance with no recognizable resistance to borrelidin A itself. |
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| Publication date | 2023-04-08 |
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| Publisher | Nature |
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| Licence | |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | c98967bf-6b4b-4ef7-a198-69512a6f3cb3 |
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| Record created | 2023-08-03 |
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| Record modified | 2023-08-03 |
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