2019 Fiscal Year Final Research Report
Mechanism, evolution and regulation of multidrug resistance
| Project/Area Number |
19K21223
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| Project/Area Number (Other) |
18H06103 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0801:Pharmaceutical sciences and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Zwama Martijn 大阪大学, 産業科学研究所, 特任助教(常勤) (40827052)
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Keywords | AcrB / Evolution / Multidrug resistance / Efflux pump / Pathogens / Phylogenesis / Haemophilus influenzae / Efflux pump inhibitor |
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| Outline of Final Research Achievements |
With this research, I was able to analyze the evolution of RND-type multidrug efflux pumps and provide insights into drug and efflux pump inhibitor specificity. I found that an ancient efflux pump (AcrB-Hi) can export the same range of antibiotics and an evolved pump (AcrB-Ec), from different bacteria, Haemophilus influenzae and Escherichia coli, respectively. However, there were some important differences observed. AcrB-Hi was not able to export bile salts efficiently, as opposed to AcrB-Ec. Additionally, AcrB-Hi was uninhibited by an efflux pump inhibitor, which inhibited AcrB-Ec completely. The drug sensitivity to certain drugs of H. influenzae cells could be explained by the presence of a large outer membrane protein. These results provide important insights for the development of novel antibiotics and efflux pump inhibitors.
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| Free Research Field |
細菌学
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| Academic Significance and Societal Importance of the Research Achievements |
The results from this research provide important insights for the development of novel antibiotics and efflux pump inhibitors. This research is of importance not only for our scientific understanding of MDR, but also for our search for new antibiotics to benefit global human health.
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