P aeruginosa Type III Cytotoxins That Modulate the Actin Cytoskeleton Rho GAP Domains of ExoS and ExoT

Rho Domein

Exoenzyme S is a bifunctional type III cytotoxin that possesses two independent activities (Fig. 1). The N terminus comprises a Rho GAP activity, whereas the C terminus comprises an ADP-ribosyltransferase activity. Iglewski and coworkers discovered ExoS as a second ADP-ribosylating protein that was produced by P. aeruginosa 28 . ExoS ADP-ribosylated Ras and several related GTPases 9 , with subsequent studies showing that ADP-ribosylation of RasatArg41 disrupted Ras interactions with its GEF 19...

Introduction

Invasive bacteria are not the passive victims of phagocytosis and the phagocyte killing machinery depicted in the past. They are, on the contrary, quite robust in defending themselves against the host's immune system, and they have developed elegant defense strategies to promote their survival (reviewed in Cornelis 2002 Cosart and Sansonetti 2004 Sibley 2004). As discussed in detail in other chapters in this volume, some bacteria have developed ingenious mechanisms to avert phagocytosis,...

H pylori Partial Inhibition of Phagocytosis and Intracellular Survival

An increased number of T lymphocytes, macrophages, and polymorphonu-clear leukocytes are evident in histological sections of gastric mucosa from patients with H. pylori infections (Kazi et al. 1989). Despite the presence of these phagocytes, H. pylori can persist several decades, suggesting the existence of a resistance mechanism to phagocytosis. H.pylori is capable of inhibiting its internalization into the host cells (Ramarao et al. 2000). This requires the presence of the type IV secretion...

Small GTPases and Bacterial Virulence Strategies

As discussed above and seen throughout this volume, small Rho GTPases are utilized extensively by bacterial pathogens to usurp normal cellular processes as part of virulence. This is presumably because of their central role in cellular functions and their many diverse downstream effects. These virulence factors generally fall into two categories toxins that bind to cellular surfaces and can be internalized into host cells and effector proteins that are injected via type III and type IV...

Nucleotide Exchange Catalyzed by SopE Versus EDTA

It is quite interesting to observe that SopE78-240 -catalyzed G-nucleotide release can proceed at higher rates (fccat) than G-nucleotide release in the presence of EDTA 4, 33, 37 . The latter reaction is commonly used for loading G-binding proteins with new nucleotides or as a control for G-nucleotide release experiments. The different G-release rates obtained with a Mg2+ chelator (EDTA) and SopE can be rationalized if one considers the underlying catalytic mechanisms. These are quite...

Phagocytosis The Lesser Evil

In light of the ROS generated and the proteases that are active in the phago-some, phagocytosis would certainly seem to be a death sentence for many bacteria. Yet a number of bacteria manage to escape death by converting the phagosome from a death chamber into a refuge. These bacteria carry out covert operations that we are only beginning to understand that allow their survival within the phagosome (Allen 2003 Cosart and Samsonetti 2004 Rosen 2004). These include preventing fusion of the...

Hpylori Infection Inflammation and Epithelial Cell Scattering

An important part of tissue damage triggered by H. pylori is thought to occur as an indirect consequence of the inflammation induced by the bacteria. In addition, H. pylori plays a more direct role in this process by triggering the dissociation, migration, and remodeling of epithelial monolayers, A process reminiscent of the effects induced by the hepatocyte growth factor (HGF) (Churin et al. 2001 Segal et al. 1999). H. pylori-Triggered Signaling Leading to Gene Transcription Regulation and...

Rho GTPases in Lymphocyte Circulation and Motility

T cells are mobile cells trafficking throughout the body to scan for exogenous antigens. During the development of immune responses and before interacting with APCs, activated T cells respond to chemokine signals that attract them from the blood into target inflamed tissue in a process called extravasation (reviewed in Barreiro et al. 2004). This process is also important during the constant recirculation of unchallenged T cells throughout the lymphoid organs (Campbell et al. 1998, 2003)....

UPEC Persistence in a Mouse Cystitis Model

In vitro experiments first suggested that UPEC may be intracellular, and gentamicin invasion assays revealed that about 3 of cell-associated UPEC are intracellular after 1 h of infection (Martinez et al. 2000). Invasion requires the expression of the type I pilus and, more specifically, the FimH adhesin at the tip of the pilus. Furthermore, this protein coated on beads is sufficient for efficient internalization (50 internalized beads). Internal-ization is inhibited by compactin, a general...

Host Cell Invasion via the Trigger Mechanism The Salmonella Paradigm

Salmonella Invasion

Salmonella spp. are gram-negative rods that cause foodborne infections, worldwide. After ingestion of contaminated food, the bacteria reach the gut, where they trigger diarrhea and invade the intestinal mucosa. The latter process can be simulated in tissue culture Five to fifteen minutes after addition of Salmonella enterica subspecies 1 serovar Typhimurium S. Typhimurium to fibroblasts and many other nonphagocytic cell lines the bacteria induce profound cytoskeletal rearrangements in the...

EPEC Filopodia Formation and Invasion

Several publications reported in vitro and sometimes in vivo internalization of EPEC or EHEC strains Donnenberg et al. 1989 Donnenberg and Kaper 1992 . Conditions can be found in which reproducible invasion of about 10 of adhering bacteria occurs after 60-min infection Jepson et al. 2003 . Although the clinical significance of this process is not clear, most isolates present this property Donnenberg et al. 1989 and several studies have attempted to identify the mechanisms involved in this...

The Pivotal Role of Rac2 in Adhesion Mediated Suppression of ROS in Neutrophils

In addition to being a regulatory component of electron flow of the NADPH oxidase, Rac2 serves as a common point of convergence for integrin and chemoattractant receptor cross talk in neutrophils Zhao et al. 2003 . Neu-trophils that were adherent to fibronectin- or fibrinogen-coated tissue culture plates were observed to have an oxidative burst that was delayed by 30-90 min after stimulation with formyl-methionyl leucyl phenylalanine fMLF peptide or C5a. The delay has been shown to be a result...