| Project/Area Number |
23K14346
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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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, 特任准教授(常勤) (40827052)
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| Project Period (FY) |
2023-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | RND / Transporter / Multidrug Resistance / MDR / Efflux Pump / Pathogens |
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| Outline of Research at the Start |
Summary: Study RND-type efflux pumps in A. baumannii and P. aeruginosa.
Outline: Investigate three efflux pump complexes in A. baumannii, test inhibitors, sequence for substitutions, and create knockouts and chimeras. Compare P. aeruginosa's MexD and MexF pumps, create chimera proteins, and express pumps in knockouts to test MIC spectra, inhibition, and stability. Create AdeABC, AdeFGH, and AdeIJK knockouts for Japanese isolates. Transform plasmids to compare substrate specificity and inhibitors. Perform MIC experiments and export assays with efflux pump inhibitors.
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| Outline of Annual Research Achievements |
One of the leading causes of clinical multidrug-resistant (MDR) bacterial hospital isolates is the over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-cell Division (RND) protein superfamily. We aimed to understand the roles of efflux pumps in clinical isolates to MDR and also study less-studied clinically relevant pumps. During the first fiscal year of this research project, we started the first cloning of RND-type efflux pumps for this project and created active pumps. The results show interesting, novel findings that are relevant and important to the field of multidrug resistance. The preliminary results were very interesting, and we are currently continuing to investigate the phenotypes to help us understand multidrug resistance caused by the RND-type efflux pumps of P. aeruginosa, E. coli, and A. baumannii. Gene expression analysis was also performed, which gave us detailed information about the resistance factors in the resistant bacteria. In this fiscal year, we were also able to publish three papers, including drafting multiple manuscripts and laying the groundwork for additional research and publications in the near future, likely for the next fiscal year.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
The research went smoothly because there were no problems with cloning, and experimental results showed interesting preliminary results already.
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| Strategy for Future Research Activity |
Continue with the research as planned and perform experiments based on the positive procedures and results.
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