| Project/Area Number |
23K14521
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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 49050:Bacteriology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Pratama Andre 大阪大学, 微生物病研究所, 特任研究員(常勤) (30972319)
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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: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | Vibrio parahaemolyticus / T3SS / gene regulation / virulence |
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| Outline of Research at the Start |
The major seafood-borne pathogen Vibrio parahaemolyticus senses bile as a chemical cue in the intestine to activate the T3SS2, which is responsible for its enterotoxicity but represses the T3SS1 activity. In this study, the applicant tries to understand how bile affects T3SS1 repression. To this end, the responsible molecule will be identified and characterized using biochemistry and molecular biology techniques to understand this regulatory mechanism.
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| Outline of Annual Research Achievements |
Pathogenic Vibrio parahaemolyticus causes septicemia and acute gastroenteritis in humans, by utilizing nano weapons called Type 3 Secretion Systems (T3SSs). This bacterium encoded two T3SSs called T3SS1 and T3SS2, whose expression is dictated by certain signals from the surrounding environment. It has been reported that bile, a compound found in the human intestine, acts as a chemical cue to trigger T3SS2 expression while also shutting off T3SS1 expression. In this study, the applicant tries to understand how bile affects T3SS1 repression.
During the first year, the applicant identified conjugated secondary bile acids, which are human metabolites found within bile, as a signal that represses T3SS1. The applicant investigated potential regulators that could serve as a signal for these molecules by examining the gene and protein expression of those regulator mutants in the context of T3SS1. As a result, one regulator (regulator X) is a key factor in this phenomenon. Furthermore, using the transcriptomic analysis, many genes were differentially expressed by regulator X besides T3SS1 downregulation. However, careful examination revealed that regulator X indirectly repressed the T3SS1. To find the direct repressor, the applicant created an expression library of genes activated by regulator X for screening and found genes A, B, and C linked to T3SS1 activity.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
According to the research timeline for the first year, the applicant's objective was to identify the responsible molecules for T3SS1 repression. The results showed that three responsible molecules were identified and validated.
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| Strategy for Future Research Activity |
Following the applicant’s plan, the next step involves characterizing and elucidating the identified molecules, aiming to understand how these molecules cause T3SS1 repression in the hope of revealing the molecular mechanism behind this phenomenon.
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