entry into host cells: the work in concert of type III secreted effector proteins

Zhou, Daoguo; Galán, Jorge E.

doi:10.1016/s1286-4579(01)01489-7

Cited by 276 publications

(239 citation statements)

References 55 publications

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“…For example, P. aeruginosa, Yersinia, and Salmonella produce GTPase-activating proteins and proteases (ExoS/T, SptP/YopE, and YopT, respectively) that inactivate small monomeric GTPases such as Rho, Rac, and Cdc42 (7,40,41). Salmonella also produces effectors, which act as guanine exchange factors to activate GTPases (SopE/E2), and actin polymerizing/depolymerizing (SipA/ADF, cofilin) enzymes, to control actin filament assembly/disassembly (42). Yersinia translocates a tyrosine phosphatase (43), YopH, which acts at focal adhesions (44), whereas ExoT ADP-ribosyltransferase of P. aeruginosa targets the Crk proteins (12), also components of focal adhesion complexes.…”

Section: Discussionmentioning

confidence: 99%

Ezrin/Radixin/Moesin Proteins Are High Affinity Targets for ADP-ribosylation by Pseudomonas aeruginosa ExoS

Maresso

Baldwin

Barbieri

2004

Journal of Biological Chemistry

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Pseudomonas aeruginosa ExoS is a bifunctional type III-secreted cytotoxin. The N terminus (amino acids 96 -233) encodes a GTPase-activating protein activity, whereas the C terminus (amino acids 234 -453) encodes a factor-activating ExoS-dependent ADP-ribosyltransferase activity. The GTPase-activating protein activity inactivates the Rho GTPases Rho, Rac, and Cdc42 in cultured cells and in vitro, whereas the ADP-ribosylation by ExoS is poly-substrate-specific and includes Ras as an early target for ADP-ribosylation. Infection of HeLa cells with P. aeruginosa producing a GTPase-activating protein-deficient form of ExoS rounded cells, indicating the ADP-ribosyltransferase domain alone is sufficient to elicit cytoskeletal changes. Examination of substrates modified by type III-delivered ExoS identified a 70-kDa protein as an early and predominant target for ADP-ribosylation. Matrix-assisted laser desorption ionization mass spectroscopy identified this protein as moesin, a member of the ezrin/radixin/moesin (ERM) family of proteins. ExoS ADP-ribosylated recombinant moesin at a linear velocity that was 5-fold faster and with a K m that was 2 orders of magnitude lower than Ras. Moesin homologs ezrin and radixin were also ADPribosylated, indicating the ERMs collectively represent high affinity targets of ExoS. Type III delivered ExoS ADP-ribosylated moesin and ezrin (and/or radixin) in cultured HeLa cells. The ERM proteins contribute to cytoskeleton dynamics, and the ability of ExoS to ADPribosylate the ERM proteins links ADP-ribosylation with the cytoskeletal changes associated with ExoS intoxication.

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Section: Discussionmentioning

confidence: 99%

Ezrin/Radixin/Moesin Proteins Are High Affinity Targets for ADP-ribosylation by Pseudomonas aeruginosa ExoS

Maresso

Baldwin

Barbieri

2004

Journal of Biological Chemistry

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“…PI gene expression is generally limited to specific host compartments. They often "plug" in to endogenous two-component housekeeping regulators to "sense" where they are within a host and regulate expression accordingly (12). Two major PIs encode type three secretion system (TTSS) that translocates bacterial virulence proteins into host cells during infections (12) (Figure 1).…”

Section: Molecular and Biologic Features Of Salmonella Typhimentioning

confidence: 99%

“…The TTSS and its effectors encoded by Salmonella pathogenesis island 1 (SPI-1) are required for invasion of epithelial cells (12) and is activated under conditions thought to be present in the intestinal lumen before host cell invasion (13). The SPI-1 secreted effectors SopE and SopE2 act as guanine-nucleotide-exchange-factors (GEFs) for the small GTPases Cdc42 and Rac (14) (Figure 2).…”

Section: Molecular and Biologic Features Of Salmonella Typhimentioning

confidence: 99%

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

2008

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Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular & Molecular Immunology. 2008;5(2):91-97.

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“…The bacterium first injects, via the type III secretion system the Rho-GEF SopE into cell to activate actin remodeling and later injects the Rho-GAP SptP to finish the uptake. 61 One can conclude that the separation of GEF and GAP activity in space and/or time is a general principle for small (and large) GTP-binding proteins which should be in place to avoid futile cycles of GTP hydrolysis.…”

Section: Resultsmentioning

confidence: 99%