Specific Behavior of Intracellular Streptococcus pyogenes That Has Undergone Autophagic Degradation Is Associated with Bacterial Streptolysin O and Host Small G Proteins Rab5 and Rab7

被引：63

作者：

Sakurai, Atsuo ^{[1
,2
]}

Maruyama, Fumito ^{[4
]}

Funao, Junko ^{[1
]}

Nozawa, Takashi ^{[5
,6
]}

Aikawa, Chihiro ^{[5
,6
]}

Okahashi, Nobuo ^{[7
]}

Shintani, Seikou ^{[2
,3
]}

Hamada, Shigeyuki ^{[8
]}

Ooshima, Takashi ^{[1
]}

Nakagawa, Ichiro ^{[6
]}

机构：

[1] Osaka Univ, Grad Sch Dent, Dept Pediat Dent, Suita, Osaka 5650871, Japan

[2] Tokyo Dent Coll, Dept Pediat Dent, Mihama Ku, Chiba 2618502, Japan

[3] Tokyo Dent Coll, Oral Hlth Sci Ctr, Hrc7, Mihama Ku, Chiba 2618502, Japan

[4] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Informat, Midori Ku, Yokohama, Kanagawa 2268501, Japan

[5] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Bacterial Pathogenesis, Bunkyo Ku, Tokyo 1138510, Japan

[6] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan

[7] Osaka Univ, Grad Sch Dent, Dept Oral Frontier Biol, Suita, Osaka 5650871, Japan

[8] Minist Publ Hlth, Res Collaborat Ctr Emerging & Reemerging Infect R, Dept Med Sci, Muang Nonthaburi 11000, Thailand

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 29期

基金：

日本学术振兴会;

关键词：

GROUP-A STREPTOCOCCUS; FIBRONECTIN-BINDING PROTEIN; LISTERIA-MONOCYTOGENES; EPITHELIAL-CELLS; MAMMALIAN-CELLS; RECEPTOR; PATHWAYS; SURVIVAL; STRAINS; GROWTH;

D O I：

10.1074/jbc.M109.100131

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Streptococcus pyogenes (group A streptococcus (GAS)) is a pathogen that invades non-phagocytic host cells, and causes a variety of acute infections such as pharyngitis. Our group previously reported that intracellular GAS is effectively degraded by the host-cell autophagic machinery, and that a cholesterol-dependent cytolysin, streptolysin O (SLO), is associated with bacterial escape from endosomes in epithelial cells. However, the details of both the intracellular behavior of GAS and the process leading to its autophagic degradation remain unknown. In this study, we found that two host small G proteins, Rab5 and Rab7, were associated with the pathway of autophagosome formation and the fate of intracellular GAS. Rab5 was involved in bacterial invasion and endosome fusion. Rab7 was clearly multifunctional, with roles in bacterial invasion, endosome maturation, and autophagosome formation. In addition, this study showed that the bacterial cytolysin SLO supported the escape of GAS into the cytoplasm from endosomes, and surprisingly, a SLO-deficient mutant of GAS was viable longer than the wild-type strain although it failed to escape the endosomes. This intracellular behavior of GAS is unique and distinct from that of other types of bacterial invaders. Our results provide a new picture of GAS infection and host-cell responses in epithelial cells.

引用

页码：22666 / 22675

页数：10