Use of a novel coinfection system reveals a role for Rac1, H-Ras, and CrkII phosphorylation in Helicobacter pylori-induced host cell actin cytoskeletal rearrangements

被引:29
作者
Brandt, Sabine
Shafikhani, Sasha
Balachandran, Priya
Jin, Shouguang
Hartig, Roland
Koenig, Wolfgang
Engel, Joanne
Backert, Steffen
机构
[1] Otto Von Guericke Univ, Dept Med Microbiol, D-39120 Magdeburg, Germany
[2] Univ Calif San Francisco, Program Microbial Pathogenesis & Host Def, Dept Med, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Program Microbial Pathogenesis & Host Def, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[4] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA
[5] Univ Magdeburg, Dept Immunol, D-39106 Magdeburg, Germany
来源
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY | 2007年 / 50卷 / 02期
关键词
molecular pathogenesis; pathogenicity island; toxin; type III and type IV secretion; Helicobacter pylori; Pseudomonas aeruginosa;
D O I
10.1111/j.1574-695X.2007.00234.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The Helicobacter pylori CagA protein induces profound morphological changes in the host cytoskeleton and cell scattering, but the signalling involved is poorly understood. Pseudomonas aeruginosa also affects host actin cytoskeleton in a variety of ways by injecting the ExoS and ExoT toxins which encode N-terminal GTPase activating protein and C-terminal ADP-ribosyltransferase (ADPRT) activities. In this study we developed a novel coinfection assay to gain new insights into CagA effector protein functions. We found that P. aeruginosa injecting either ExoT or ExoS efficiently prevented the H. pylori-induced scattering phenotype. Both the Rho-GAP and the ADPRT domains of ExoS were needed to block the H. pylori-induced actin cytoskeletal rearrangements, whereas either domain of ExoT was sufficient for this activity. This strategy revealed common pathways subverted by different pathogens, and aided in the definition of signalling cascades that control the CagA-mediated cell scattering and elongation. We identified Crk adapter proteins, Rac1 and H-Ras, but not RhoA or Cdc42, which are the ExoS and/or ExoT targets, as crucial components of the CagA-induced phenotype. In addition, we show that ADP-ribosylation of CrkII by ExoT blocks phosphorylation of CrkII at Y-221, which is also important for the CagA-induced signalling.
引用
收藏
页码:190 / 205
页数:16
相关论文
共 52 条
[1]   Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling [J].
Abassi, YA ;
Vuori, K .
EMBO JOURNAL, 2002, 21 (17) :4571-4582
[2]   ExoS of Pseudomonas aeruginosa induces apoptosis through a Fas receptor/caspase 8-independent pathway in HeLa cells [J].
Alaoui-El-Azher, M ;
Jia, JH ;
Lian, W ;
Jin, SG .
CELLULAR MICROBIOLOGY, 2006, 8 (02) :326-338
[3]   Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA [J].
Amieva, MR ;
Vogelmann, R ;
Covacci, A ;
Tompkins, LS ;
Nelson, WJ ;
Falkow, S .
SCIENCE, 2003, 300 (5624) :1430-1434
[4]   Type IV secretion systems and their effectors in bacterial pathogenesis [J].
Backert, S ;
Meyer, TF .
CURRENT OPINION IN MICROBIOLOGY, 2006, 9 (02) :207-217
[5]   Conjugative plasmid DNA transfer in Helicobacter pylori mediated by chromosomally encoded relaxase and traG-like proteins [J].
Backert, S ;
Kwok, T ;
König, W .
MICROBIOLOGY-SGM, 2005, 151 :3493-3503
[6]   Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer [J].
Backert, S ;
Schwarz, T ;
Miehlke, S ;
Kirsch, C ;
Sommer, C ;
Kwok, T ;
Gerhard, M ;
Goebel, UB ;
Lehn, N ;
Koenig, W ;
Meyer, TF .
INFECTION AND IMMUNITY, 2004, 72 (02) :1043-1056
[7]   Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells [J].
Backert, S ;
Moese, S ;
Selbach, M ;
Brinkmann, V ;
Meyer, TF .
MOLECULAR MICROBIOLOGY, 2001, 42 (03) :631-644
[8]   ADP-ribosylation of Rab5 by ExoS of Pseudomonas aeruginosa affects endocytosis [J].
Barbieri, AM ;
Sha, Q ;
Bette-Bobillo, P ;
Stahl, PD ;
Vidal, M .
INFECTION AND IMMUNITY, 2001, 69 (09) :5329-5334
[9]   Pseudomonas aeruginosa ExoS and ExoT [J].
Barbieri, JT ;
Sun, J .
REVIEWS OF PHYSIOLOGY, BIOCHEMICAL AND PHARMACOLOGY, VOL 152, 2005, 152 :79-92
[10]   Agents that inhibit Rho, Rac, and Cdc42 do not block formation of actin pedestals in HeLa cells infected with enteropathogenic Escherichia coli [J].
Ben-Ami, G ;
Ozeri, V ;
Hanski, E ;
Hofmann, F ;
Aktories, K ;
Hahn, KM ;
Bokoch, GM ;
Rosenshine, I .
INFECTION AND IMMUNITY, 1998, 66 (04) :1755-1758