| Project/Area Number |
19K16653
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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 | Hokkaido University (2020-2021)
Teikyo University (2019) |
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Principal Investigator |
Paudel Atmika 北海道大学, 人獣共通感染症国際共同研究所, 助教 (80832774)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | pathogenesis / virulence / virulence factor / silkworm / infection / Bombyx mori / Bacillus cereus / Staphylococcus aureus / pathogenecity / host-pathogen / silkworm infection model / Pathogenicity / anti-infective agents |
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| Outline of Research at the Start |
The research will include the characterization of the proteins of S. aureus involved in pathogenesis. The elucidated functions of the proteins can then be exploited as the novel targets for the development of novel anti-infective agents. Besides availability of novel antimicrobial agents against multidrug-resistant S. aureus, the added advantage of such agents is selectiveness towards pathogen exerting lower pressure to S. aureus itself, hence, chances of emergence of resistance to such agents are low and spare the host microbiota.
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| Outline of Final Research Achievements |
We screened Nebraska Transposon Mutant Library of USA300 and found that 8 mutants with reduced virulence in silkworm and mice infection models. The pathogenicity was not restored by introduction of one of the genes: yjbI, while the introduction of the downstream gene yjbH complemented the pathogenicity in silkworms and mice. RNA-seq analysis of yjbI::Tn and yjbH::Tn mutants revealed that disruption of both genes significantly affected the expression of > 200 genes including downregulation of several virulence genes. We,theb, established silkworm infection models of Bacillus anthracis and B. cereus. Constructing a mutant library of Bacillus cereus, we found one gene X to have role in virulence in silkworm. We then used the mutants with transposon inserted in the gene X from the NTML library of S. aureus and found that the disruption of the gene X made S. aureus hyper virulent. Thus, we found that although the gene was conserved among S. aureus and B. cereus and had role in virulence.
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| Academic Significance and Societal Importance of the Research Achievements |
The research identified novel virulence factors of a Gram-positive bacteria, methicillin-resistant Staphylococcus aureus, using silkworm infection model and deepened our understanding of its pathogenicity.
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