Cajanin stilbene acid: A direct inhibitor of colistin resistance protein MCR-1 that restores the efficacy of polymyxin B against resistant Gram-negative bacteria
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Yue Jia
- Juzhao Liu
- Qin Yang
- Wanjiang Zhang
- Thomas Efferth
- Siguo Liu
- Xin Hua
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000981776200001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2023.154803
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: F4AA5
- PubMed Identifier: 37058946
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Cajanin stilbene acid
- Direct inhibitor
- Gram-negative bacteria
- MCR-1
- Sensitivity recovery
- Artikelnummer
- ARTN 154803
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- Cajanin stilbene acid: A direct inhibitor of colistin resistance protein MCR-1 that restores the efficacy of polymyxin B against resistant Gram-negative bacteria
- Sub types
- Article
- Ausgabe der Zeitschrift
- 114
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Yue Jia
- Juzhao Liu
- Qin Yang
- Wanjiang Zhang
- Thomas Efferth
- Siguo Liu
- Xin Hua
- DOI
- 10.1016/j.phymed.2023.154803
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Artikelnummer
- 154803
- Paginierung
- 154803 - 154803
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2023.154803
- Datum der Datenerfassung
- 2024
- Titel
- Cajanin stilbene acid: A direct inhibitor of colistin resistance protein MCR-1 that restores the efficacy of polymyxin B against resistant Gram-negative bacteria
- Ausgabe der Zeitschrift
- 114
Data source: Crossref
- Abstract
- <h4>Background</h4>The resistance of Gram-negative bacteria to polymyxin B, caused by the plasmid-mediated colistin resistance gene mcr-1, which encodes a phosphoethanolamine transferase (MCR-1), is a serious threat to global public health. Therefore, it is urgent to find new drugs that can effectively alleviate polymyxin B resistance. Through the screening of 78 natural compounds, we found that cajanin stilbene acid (CSA) can significantly restore the susceptibility of polymyxin B to mcr-1 positive Escherichia coli (E. coli).<h4>Purpose</h4>In this study, we tried to evaluate the ability of CSA to restore the susceptibility of polymyxin B towards the E. coli, and explore the mechanism of sensitivity recovery.<h4>Study design and methods</h4>Checkerboard MICs, time-killing curves, scanning electron microscope, lethal and semi-lethal models of infection in mice were used to assess the ability of CSA to restore the susceptibility of polymyxyn to E. coli. The interaction between CSA and MCR-1 was evaluated using surface plasmon resonance (SPR), and molecular docking experiments.<h4>Results</h4>Here, we find that CSA, a potential direct inhibitor of MCR-1, effectively restores the sensitivity of E. coli to polymyxin B. CSA can restore the sensitivity of polymyxin B to drug-resistant E. coli, and the MIC value can be reduced to 1 μg/ml. The time killing curve and scanning electron microscopy results also showed that CSA can effectively restore polymyxin B sensitivity. In vivo experiments showed that the simultaneous use of CSA and polymyxin B can effectively reduce the infection of drug-resistant E. coli in mice. SPR and molecular docking experiments confirmed that CSA strongly bound to MCR-1. The 17-carbonyl oxygen and 12- and 18‑hydroxyl oxygens of CSA were the key sites binding to MCR-1.<h4>Conclusion</h4>CSA is able to significantly restore the sensitivity of polymyxin B to E. coli in vivo and in vitro. CSA inhibits the enzymatic activity of the MCR-1 protein by binding to key amino acids at the active center of the MCR-1 protein.
- Addresses
- Division of Bacterial Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences Harbin, China.
- Autoren
- Yue Jia
- Juzhao Liu
- Qin Yang
- Wanjiang Zhang
- Thomas Efferth
- Siguo Liu
- Xin Hua
- DOI
- 10.1016/j.phymed.2023.154803
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 37058946
- Funding acknowledgements
- Natural Science Foundation of Heilongjiang Province: YQ2020C020
- National Key Research and Development Program of China: 2021YFD1800403
- Fundamental Research Funds for the Central Universities: 2572020BD01
- Fundamental Research Funds for the Central Universities:
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Animals
- Mice
- Escherichia coli
- Colistin
- Polymyxin B
- Escherichia coli Proteins
- Anti-Bacterial Agents
- Microbial Sensitivity Tests
- Drug Resistance, Bacterial
- Plasmids
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2023
- Paginierung
- 154803
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Datum der Datenerfassung
- 2023
- Titel
- Cajanin stilbene acid: A direct inhibitor of colistin resistance protein MCR-1 that restores the efficacy of polymyxin B against resistant Gram-negative bacteria.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 114
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: The resistance of Gram-negative bacteria to polymyxin B, caused by the plasmid-mediated colistin resistance gene mcr-1, which encodes a phosphoethanolamine transferase (MCR-1), is a serious threat to global public health. Therefore, it is urgent to find new drugs that can effectively alleviate polymyxin B resistance. Through the screening of 78 natural compounds, we found that cajanin stilbene acid (CSA) can significantly restore the susceptibility of polymyxin B to mcr-1 positive Escherichia coli (E. coli). PURPOSE: In this study, we tried to evaluate the ability of CSA to restore the susceptibility of polymyxin B towards the E. coli, and explore the mechanism of sensitivity recovery. STUDY DESIGN AND METHODS: Checkerboard MICs, time-killing curves, scanning electron microscope, lethal and semi-lethal models of infection in mice were used to assess the ability of CSA to restore the susceptibility of polymyxyn to E. coli. The interaction between CSA and MCR-1 was evaluated using surface plasmon resonance (SPR), and molecular docking experiments. RESULTS: Here, we find that CSA, a potential direct inhibitor of MCR-1, effectively restores the sensitivity of E. coli to polymyxin B. CSA can restore the sensitivity of polymyxin B to drug-resistant E. coli, and the MIC value can be reduced to 1 μg/ml. The time killing curve and scanning electron microscopy results also showed that CSA can effectively restore polymyxin B sensitivity. In vivo experiments showed that the simultaneous use of CSA and polymyxin B can effectively reduce the infection of drug-resistant E. coli in mice. SPR and molecular docking experiments confirmed that CSA strongly bound to MCR-1. The 17-carbonyl oxygen and 12- and 18‑hydroxyl oxygens of CSA were the key sites binding to MCR-1. CONCLUSION: CSA is able to significantly restore the sensitivity of polymyxin B to E. coli in vivo and in vitro. CSA inhibits the enzymatic activity of the MCR-1 protein by binding to key amino acids at the active center of the MCR-1 protein.
- Date of acceptance
- 2023
- Autoren
- Yue Jia
- Juzhao Liu
- Qin Yang
- Wanjiang Zhang
- Thomas Efferth
- Siguo Liu
- Xin Hua
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/37058946
- DOI
- 10.1016/j.phymed.2023.154803
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Cajanin stilbene acid
- Direct inhibitor
- Gram-negative bacteria
- MCR-1
- Sensitivity recovery
- Animals
- Mice
- Colistin
- Polymyxin B
- Anti-Bacterial Agents
- Escherichia coli
- Molecular Docking Simulation
- Drug Resistance, Bacterial
- Microbial Sensitivity Tests
- Escherichia coli Proteins
- Plasmids
- Sprache
- eng
- Country
- Germany
- Paginierung
- 154803
- PII
- S0944-7113(23)00164-2
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- Cajanin stilbene acid: A direct inhibitor of colistin resistance protein MCR-1 that restores the efficacy of polymyxin B against resistant Gram-negative bacteria.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 114
Data source: PubMed
- Beziehungen:
- Property of