A Vibrio Effector Protein Is an Inositol Phosphatase and Disrupts Host Cell Membrane Integrity

被引:90
作者
Broberg, Christopher A. [1 ]
Zhang, Lingling [1 ]
Gonzalez, Herman [1 ]
Laskowski-Arce, Michelle A. [1 ]
Orth, Kim [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
关键词
PARAHAEMOLYTICUS; AUTOPHAGY; BINDING; DOMAINS; GENOME;
D O I
10.1126/science.1192850
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The marine bacterium Vibrio parahaemolyticus causes gastroenteritis in humans and encodes the type III effector protein VPA0450, which contributes to host cell death caused by autophagy, cell rounding, and cell lysis. We found that VPA0450 is an inositol polyphosphate 5-phosphatase that hydrolyzed the D5 phosphate from the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate. VPA0450 disrupted cytoskeletal binding sites on the inner surface of membranes of human cells and caused plasma membrane blebbing, which compromised membrane integrity and probably contributed to cell death by facilitating lysis. Thus, bacterial pathogens can disrupt adaptor protein-binding sites required for proper membrane and cytoskeleton dynamics by altering the homeostasis of membrane-bound inositol-signaling molecules.
引用
收藏
页码:1660 / 1662
页数:3
相关论文
共 20 条
[1]   Tipping the balance by manipulating post-translational modifications [J].
Broberg, Christopher A. ;
Orth, Kim .
CURRENT OPINION IN MICROBIOLOGY, 2010, 13 (01) :34-40
[2]   Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis [J].
Burdette, Dara L. ;
Yarbrough, Melanie L. ;
Orvedahl, Anthony ;
Gilpin, Christopher J. ;
Orth, Kim .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (34) :12497-12502
[3]   Vibrio VopQ induces PI3-kinase-independent autophagy and antagonizes phagocytosis [J].
Burdette, Dara L. ;
Seemann, Joachim ;
Orth, Kim .
MOLECULAR MICROBIOLOGY, 2009, 73 (04) :639-649
[4]   Blebs lead the way: how to migrate without lamellipodia [J].
Charras, Guillaume ;
Paluch, Ewa .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (09) :730-736
[5]   The type III secretion injectisome [J].
Cornelis, Guy R. .
NATURE REVIEWS MICROBIOLOGY, 2006, 4 (11) :811-825
[6]   PIP2 and PIP3: Complex roles at the cell surface [J].
Czech, MP .
CELL, 2000, 100 (06) :603-606
[7]   Vibrio parahaemolyticus infections in the United States, 1973-1998 [J].
Daniels, NA ;
MacKinnon, L ;
Bishop, R ;
Altekruse, S ;
Ray, B ;
Hammond, RM ;
Thompson, S ;
Wilson, S ;
Bean, NH ;
Griffin, PM ;
Slutsker, L .
JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (05) :1661-1666
[8]   Phosphoinositides in cell regulation and membrane dynamics [J].
Di Paolo, Gilbert ;
De Camilli, Pietro .
NATURE, 2006, 443 (7112) :651-657
[9]   Common Themes in the Design and Function of Bacterial Effectors [J].
Galan, Jorge E. .
CELL HOST & MICROBE, 2009, 5 (06) :571-579
[10]   Signaling and subcellular targeting by membrane-binding domains [J].
Hurley, JH ;
Misra, S .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2000, 29 :49-79