| 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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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | AcrB / Evolution / Multidrug resistance / Efflux pump / Pathogens / Phylogenesis / Haemophilus influenzae / Efflux pump inhibitor / Regulation / Bacteria / Transporters / RND / Transporter / Antibiotic / Resistance |
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| Outline of Research at the Start |
This research is focussed on the study of multidrug efflux pumps from Legionella pneumophila. The main goal is to clone and study multiple efflux pumps and analyze their antibiotic transport ability, and gain insights in potential clinically relevant Multidrug resistant Legionella pneumophila pathogenic strains.
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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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| 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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