The role of RNA binding protein Hfq on the virulence factor of periodontal pathogen

Research Project

Project/Area Number	19K19027
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 57030:Conservative dentistry-related
Research Institution	Okayama University
Principal Investigator	Hirai Kimito 岡山大学, 医歯薬学総合研究科, 助教 (10710171)
Project Period (FY)	2019-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	Hfq / small RNA / A. actinomycetemcomitans / 歯周病 / 感染性心内膜炎 / Cell adhision / 歯周炎 / RNA binding protein / biofilm formation / RNA chaperone
Outline of Research at the Start	RNA結合タンパク質であるHfqは多くの菌種で保存されており，環境の変化に応じて病原因子に関わる遺伝子のmRNAとsmall RNAとの会合を仲介して転写後の発現調整を担う。Aggregatibacter actinomycetemcomitansにおいては，Hfqの役割はまったく分かっておらず，本研究ではHfqが細菌の上皮細胞への侵入，免疫細胞との反応性に関与する遺伝子をどのように制御しているかを検討する。
Outline of Final Research Achievements	Aggregatibacter actinomycetemcomitans is one of the pathobiont causing periodontal disease that is involved in infectious endocarditis. Hfq is a member of RNA binding protein and is best known for its function in post-transcriptional gene regulation by small regulatory RNA. We investigated the role of Hfq on the virulence factors of A. actinomycetemcomitans using hfq deletion mutant. On the present study, hfq deletion attenuated biofilm formation on cell culture plate coated with extra-cellular matrix and reduced invasion efficiency into epithelium cell. Furthermore, the genes expression of flp1, rcpA, rcpB, tadA that relating cell adhesion or invasion were down regulated on hfq deletion mutant compared with parent strain ATCC29523. Taken together, this present study indicated that Hfq regulate virulence factor of A. actinomycetemcomitans in the course of the bacterial adhision and invasion into the host cell.
Academic Significance and Societal Importance of the Research Achievements	今回の成果はA. actinomycetemcomitansが口腔の局所から血管内へ侵入する過程において，巧みに環境ストレスに適応しながら遺伝子の発現を制御するメカニズムの一旦を解明した。本研究対象のA. actinomycetemcomitansは，感染性心内膜炎やアテローム性動脈硬化症に関与していることは疫学的研究で明らかとなっているが，本研究はその発症の詳細なメカニズムの解明に挑戦するものであり，研究成果は今後，心臓・血管疾患の予防につながる可能性のある，社会への波及効果が大きい。