Blockade of endoplasmic reticulum stress-induced cell death by Ureaplasma parvum vacuolating factor.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osama Woman's and Children's Hospital
• Principal Investigator: Nishiumi Fumiko 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 免疫部門, 流動研究員 (60599596)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: U. parvum / ER stress / anticancer effect

Outline of Final Research Achievements

Annually, 15 million neonates are born preterm, and preterm birth complications are responsible for the deaths of 1 million children. Approximately half of the preterm cases are associated with bacterial infections. Ureaplasma spp. belongs to family Mycoplasmataceae, and is known as one of the significant causatives of preterm birth.
I reported that U. parvum internalized into host cells by clathrin-mediated endocytosis and survived at least 14 days within HeLa cells. Interestingly, intracellular U. parvum disrupted host intracellular membrane, which took part in the host cellular degradation system, including the clearance of pathogens. By using yeast vesicular trafficking inhibitory screening method, a novel Ureaplasma membrane disrupting factor (UpVF) was isolated. These findings provided a novel implication for host-pathogen interaction by one of the smallest free-living microorganisms, Ureaplasma.

Free Research Field

細菌感染、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

周産期医療最大の課題である早産抑止に向け、主要なヒト流早産原因細菌であるウレアプラズマの解析を行ってきた。ウレアプラズマには、アジスロマイシン等のマクロライド系抗菌薬が使用され一定の効果を得ているが、近年は国内でも耐性菌が多く分離される。ウレアプラズマのさらなる制御には、その病原発揮機構を詳細に明らかにする必要がある。今回の我々の解析で、ウレアプラズマは宿主細胞内に侵入し、そして宿主のオートファジーなどの膜系による分解を巧妙に回避しながら、宿主と折り合いをつけ生存していることが示された。ウレアプラズマの宿主膜系の障害には名付けた新規の病原因子UpVFが関与していた。