Translocation of a Vibrio cholerae Type VI Secretion Effector Requires Bacterial Endocytosis by Host Cells

被引:222
作者
Ma, Amy T. [1 ]
McAuley, Steven [2 ]
Pukatzki, Stefan [2 ]
Mekalanos, John J. [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA
[2] Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2H7, Canada
基金
美国国家卫生研究院;
关键词
ENTEROAGGREGATIVE ESCHERICHIA-COLI; COVALENT CROSS-LINKING; RTX TOXIN; EL-TOR; PECTOBACTERIUM-ATROSEPTICUM; BURKHOLDERIA-PSEUDOMALLEI; PATHOGENICITY ISLAND; COLONIZATION FACTOR; EDWARDSIELLA-TARDA; BETA-LACTAMASE;
D O I
10.1016/j.chom.2009.02.005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The type VI secretion system (T6SS) is a virulence mechanism common to several Gram-negative pathogens. In Vibrio cholerae, VgrG-1 is required for T6SS-dependent secretion. VgrG-1 is also secreted by T6SS and displays a C-terminal actin crosslinking domain (ACID). Using a heterologous reporter enzyme in place of the ACD, we show that the effector and secretion functions of VgrG-1 are genetically dissociable with the ACID being dispensable for secretion but required for T6SS-dependent phenotypes. Furthermore, internalization of bacteria is required for ACD translocation into phagocytic target cells. Inhibiting bacterial uptake abolishes actin crosslinking, while improving intracellular survival enhances it. Otherwise resistant nonphagocytic cells become susceptible to T6SS-mediated actin crosslinking when engineered to take up bacteria. Our results support a model for translocation of VgrG C-terminal effector domains into target cell cytosol by a process that requires trafficking of bacterial cells into an endocytic compartment where translocation is triggered by an unknown signal.
引用
收藏
页码:234 / 243
页数:10
相关论文
共 54 条
[1]   Intracellular survival and replication of Vibrio cholerae O139 in aquatic free-living amoebae [J].
Abd, H ;
Weintraub, A ;
Sandström, G .
ENVIRONMENTAL MICROBIOLOGY, 2005, 7 (07) :1003-1008
[2]   SciN Is an Outer Membrane Lipoprotein Required for Type VI Secretion in Enteroaggregative Escherichia coli [J].
Aschtgen, Marie-Stephanie ;
Bernard, Christophe S. ;
De Bentzmann, Sophie ;
Lloubes, Roland ;
Cascales, Eric .
JOURNAL OF BACTERIOLOGY, 2008, 190 (22) :7523-7531
[3]   A novel sensor kinase-response regulator hybrid controls biofilm formation and type VI secretion system activity in Burkholderia cenocepacia [J].
Aubert, Daniel F. ;
Flannagan, Ronald S. ;
Valvano, Miguel A. .
INFECTION AND IMMUNITY, 2008, 76 (05) :1979-1991
[4]   Bacterial toxins that modify the actin cytoskeleton [J].
Barbieri, JT ;
Riese, MJ ;
Aktories, K .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2002, 18 :315-344
[5]   Type VI secretion: a beginner's guide [J].
Bingle, Lewis E. H. ;
Bailey, Christopher M. ;
Pallen, Mark J. .
CURRENT OPINION IN MICROBIOLOGY, 2008, 11 (01) :3-8
[6]   Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion [J].
Boenemann, Gabriele ;
Pietrosiuk, Aleksandra ;
Diemand, Alexander ;
Zentgraf, Hanswalter ;
Mogk, Axel .
EMBO JOURNAL, 2009, 28 (04) :315-325
[7]   The Legionella pneumophila icmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation [J].
Cambronne, Eric D. ;
Roy, Craig R. .
PLOS PATHOGENS, 2007, 3 (12) :1837-1848
[8]   Identification of the secretion and translocation domain of the enteropathogenic and enterohemorrhagic Escherichia coli effector Cif, using TEM-1 β-lactamase as a new fluorescence-based reporter [J].
Charpentier, X ;
Oswald, E .
JOURNAL OF BACTERIOLOGY, 2004, 186 (16) :5486-5495
[9]   The mannose-sensitive hemagglutinin of Vibrio cholerae promotes adherence to zooplankton [J].
Chiavelli, DA ;
Marsh, JW ;
Taylor, RK .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2001, 67 (07) :3220-3225
[10]   The actin cross-linking domain of the Vibrio cholerae RTX toxin directly catalyzes the covalent cross-linking of actin [J].
Cordero, Christina L. ;
Kudryashov, Dmitry S. ;
Reisler, Emil ;
Satchell, Karla J. Fullner .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (43) :32366-32374