Disease relevance of exoS

• Expression of Pseudomonas aeruginosa exoS is controlled by quorum sensing and RpoS [1].
• With the addition of exoS and exoT to the molecular arsenal, questions concerning in vivo toxicity and target specificities of exoenzyme S can be directly addressed [2].
• The exoT open reading frame, cloned into a T7 expression system, produced a 53-kDa protein in Escherichia coli, termed Exo53, which reacted to antisera against exoenzyme S. A histidine-tagged derivative of recombinant Exo53 possessed approximately 0.2% of the ADP-ribosyltransferase activity of recombinant ExoS [3].
• By using an approach in which exoS was expressed in different strains of Yersinia, including secretion and translocation mutants, we could demonstrate that ExoS was secreted and translocated into HeLa cells by a similar mechanism to that described previously for YopE [4].
• There was no significant difference in exoU or exoS prevalence among the keratitis strains [5].

High impact information on exoS

• Exoenzyme S (ExoS), which has been implicated as a virulence factor of Pseudomonas aeruginosa, catalyzes transfer of the ADP-ribose moiety of NAD+ to many eukaryotic cellular proteins [6].
• Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyltransferase distinct from toxin A [7].
• Digestion of the radiolabeled product(s) formed in the presence of [adenine-14C]NAD+ and exoenzyme S with snake venom phosphodiesterase yields only AMP, suggesting that ADP-ribose is present as monomers and not as poly(ADP-ribose) [7].
• These latter observations and the substrate specificity suggest that exoenzyme S is different from any previously described prokaryotic ADP-ribosyltransferase [7].
• Pseudomonas aeruginosa exoenzyme S is an adenosine diphosphate ribosyltransferase distinct from Pseudomonas toxin A. Exoenzyme S catalyzes the transfer of radioactivity from all portions of radiolabeled NAD+ except nicotinamide [7].

Chemical compound and disease context of exoS

• Pseudomonas aeruginosa exoenzyme S (ExoS) ADP-ribosylated Ras to a stoichiometry of approximately 2 molecules of ADP-ribose incorporated per molecule of Ras, which suggested that ExoS could ADP-ribosylate Ras at more than one arginine residue [8].
• Pseudomonas aeruginosa exoenzyme S disrupts Ras-mediated signal transduction by inhibiting guanine nucleotide exchange factor-catalyzed nucleotide exchange [9].
• 14-3-3 binds ligands such as Raf-1 kinase and Bad by recognizing the phosphorylated consensus motif, RSXpSXP, but must bind unphosphorylated ligands, such as glycoprotein Ib and Pseudomonas aeruginosa exoenzyme S, via a different motif [10].
• Pseudomonas aeruginosa produces two distinct ADP-ribosyl transferases, exotoxin A and exoenzyme S, which differ in a number of properties including substrate specificity [11].
• The glycerolipid receptor for Helicobacter pylori (and exoenzyme S) is phosphatidylethanolamine [12].

Biological context of exoS

• Clinical isolates that injure lung epithelium in vivo and that are cytotoxic in vitro possess exoT but lack exoS, suggesting that ExoS is not the cytotoxin responsible for the pathology and cell death measured in these assays [13].
• Evidence is provided for downregulation of exoS during biofilm formation of P. aeruginosa PAO1 [1].
• Upregulation of exoS'-gfp in the PDO100 mutant could be repressed to normal level by adding C4-HSL autoinducer, indicating a negative regulatory effect of RhlR/C4-HSL on exoS expression [1].
• The aim of this study was to develop a real time RT-PCR method for the direct quantification of the transcripts of three P. aeruginosa virulence genes: exoS, lasI and algD, during the first seven days of a rat lung infection [14].
• Our results demonstrate correlations among exoU or exoS genotype, TTSS phenotype, and O serotype in bacteremic P. aeruginosa isolates [15].

Anatomical context of exoS

• Intracellular targeting of the Pseudomonas aeruginosa toxins exoenzyme S (ExoS) and exoenzyme T (ExoT) initially results in disruption of the actin microfilament structure of eukaryotic cells [16].
• Exogenous administration of an important Pseudomonas aeruginosa virulence factor, exoenzyme S (ExoS) induces potent monocyte activation leading to the production of numerous proinflammatory cytokines and chemokines [17].
• Together, these data indicate that expression of the ADP-ribosyltransferase domain of exoenzyme S is cytotoxic to eukaryotic cells [18].
• Taken together, our data suggest that exoenzyme S is a T-cell mitogen but not a superantigen [19].
• As a first step toward developing an animal model, the murine lymphocyte response to exoenzyme S was examined [20].

Associations of exoS with chemical compounds

• Exoenzyme S modifies all of its substrates at arginine residues [21].
• Exoenzyme S absolutely requires a soluble eukaryotic protein, which we have named FAS (Factor Activating exoenzyme S), in order to ADP-ribosylate all substrates [22].
• Raf-1 kinase and exoenzyme S interact with 14-3-3zeta through a common site involving lysine 49 [23].
• Exotoxin A, exoenzyme S, phospholipase C, elastase, and total protease activities were suppressed by antibiotics at concentrations as low as 1/20 of the MIC over a 24-h period in broth [24].
• Exoenzyme S differs from toxin A and diphtheria toxin in that it does not adenosine diphosphate (ADP)-ribosylate elongation factor-2, but rather catalyzes the transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide to a number of different proteins in extracts of eucaryotic cells [25].

Other interactions of exoS

• In contrast, the exoS, exoU and exoY genes were variable traits [26].
• A fimV mutant was unable to induce the expression of exoS, exoT and exsA genes under type III inducing conditions, thus exhibiting a defect in type III protein secretion [27].
• Hybridization with the toxA internal probe produced a 0.8-kb hybridizing fragment, whereas hybridization with the exoS internal probe produced either a 2.0- or a 2.3-kb hybridizing fragment [28].
• The majority of isolates (59%) were PCR-positive for exoU rather than for exoS (38%), and carried a-type fliC genes (76%) rather than b-type (24%) [29].
• In general, the rate of multidrug resistance in the exoU positive cytotoxic and serotype E (O:11) strains was significantly higher than in exoS positive invasive strains (p < 0.01) [5].

Analytical, diagnostic and therapeutic context of exoS

• To determine the genetic relationship between the two forms of exoenzyme S, exoS (encoding the 49-kDa form) was used as a probe in Southern blot analyses of P. aeruginosa chromosomal digests [3].
• The two P. aeruginosa strains used in these studies, 388 and 388delta exoS, maintained genetic identity, with the exception that strain 388delta exoS lacked production of the 49-kDa form of ExoS [30].
• Combined data from mutagenesis, regulatory, expression, and sequence analyses provide strong evidence that P. aeruginosa possesses a type III secretion apparatus which is required for the export of exoenzyme S and potentially other co-ordinately regulated proteins [31].
• The exoenzyme S (ExoS)-producing Pseudomonas aeruginosa strain, 388, and corresponding ExoS knock-out strain, 388deltaexoS, were used in a bacterial and mammalian co-culture system as a model for the contact-dependent delivery of ExoS into host cells [32].
• Exoenzyme S expression was measured in parental and mutant derivatives by Western blot (immunoblot) analysis and ADP-ribosyltransferase activity measurement [33].

References