SUMMARY This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.
Staphylococcus aureus is an important human pathogen which is implicated in a wide variety of diseases. Major determinants of the virulence of this organism include extracellular virulence factors. Staphylococcal enterotoxins (SEs) are important causative agents in staphylococcal toxic shock syndrome and food poisoning. Our study identified a novel enterotoxin, SEK, and examined its biochemical and biological properties. SEK had a molecular weight of 26,000 and an experimentally determined pI of between 7.0 and 7.5. SEK was secreted by clinical isolates of S. aureus. We demonstrated that SEK had many of the biological activities associated with the SEs, including superantigenicity, pyrogenicity, the ability to enhance the lethal effect of endotoxin, and lethality in a rabbit model when administered by subcutaneous miniosmotic pump. Recombinant SEK was shown to stimulate human CD4 ؉ and CD8 ؉ T cells in a V-specific manner; T-cells bearing V 5.1, 5.2, and 6.7 were significantly stimulated to proliferate.
Variovorax paradoxus is a microorganism of special interest due to its diverse metabolic capabilities, including the biodegradation of both biogenic compounds and anthropogenic contaminants. V. paradoxus also engages in mutually beneficial interactions with both bacteria and plants. The complete genome sequence of V. paradoxus S110 is composed of 6,754,997 bp with 6,279 predicted protein-coding sequences within two circular chromosomes. Genomic analysis has revealed multiple metabolic features for autotrophic and heterotrophic lifestyles. These metabolic diversities enable independent survival, as well as a symbiotic lifestyle. Consequently, S110 appears to have evolved into a superbly adaptable microorganism that is able to survive in ever-changing environmental conditions. Based on our findings, we suggest V. paradoxus S110 as a potential candidate for agrobiotechnological applications, such as biofertilizer and biopesticide. Because it has many associations with other biota, it is also suited to serve as an additional model system for studies of microbeplant and microbe-microbe interactions.Variovorax paradoxus is a metabolically diverse, aerobic bacterium that engages in mutually beneficial interactions with a variety of bacteria and plants. V. paradoxus belongs to the subclass of Proteobacteria and can metabolically utilize natural compounds produced by other biota, such as acyl homoserine lactones (AHLs) (25) and alkyl/aryl-sulfonates (38). This metabolic capacity suggests that Variovorax plays an essential role in the natural cycling of biogenic chemicals. Variovorax species are also able to degrade a variety of contaminants, including pesticides and crude oil-associated S-metabolites (5,19,37,41,42,46,50,51,52), often in synergistic and mutually beneficial interactions with other bacteria. In addition, a close relative of Variovorax was found to be the central, nonphotosynthetic partner within the phototrophic consortium "Chlorochromatium aggregatum" (22). Moreover, V. paradoxus is resistant to various heavy metals, including cadmium and mercury (2).V. paradoxus belongs to a group referred to as plant growthpromoting rhizobacteria (PGPR), which exert beneficial effects on plant growth. As a common plant symbiont found in the rhizosphere (2, 3), the metabolic diversity of V. paradoxus appears to be related to its role as a PGPR. By degrading toxic contaminants, this bacterium can prevent harm otherwise experienced by the plant and thus can promote plant growth. Strains of Variovorax can enhance the host plant's stress tolerance and disease resistance (2, 3) and aid in nutrient availability and uptake (38). The effectiveness of Variovorax as a PGPR is likely to be more potent because it also appears to be a good endophytic symbiont (34,36,39,43,44,45,47) and thus interacts more closely with the host plant. Conversely, endospheric habitats are known to offer microbes the advantage of a more uniform and protective niche compared to the competitive, high-stress environment of the soil (36).The diverse metabol...
Staphylococcus aureus causes a wide variety of diseases. Major virulence factors of this organism include enterotoxins (SEs) that cause both food poisoning and toxic shock syndrome. Recently, a novel SE, tentatively designated SEL, was identified in a pathogenicity island from a bovine mastitis isolate. The toxin had a molecular weight of 26,000 and an isoelectric point of 8.5. Recombinant SEL shared many biological activities with SEs, including superantigenicity, pyrogenicity, enhancement of endotoxin shock, and lethality in rabbits when administered in subcutaneous miniosmotic pumps, but the protein lacked emetic activity. T cells bearing the T-cell receptor  chain variable regions 5.1, 5.2, 6.7, 16, and 22 were significantly stimulated by recombinant SEL.Staphylococcus aureus is an important human and animal pathogen, in part due to production of superantigen exotoxins (SAgs). The spectrum of SAg-mediated illnesses ranges from relatively benign food poisoning to life-threatening toxic shock syndrome (TSS) (2, 7). The major secreted SAgs of S. aureus include TSS toxin 1 (TSST-1) and enterotoxin (SE) serotypes A to Q, excluding F.Crystallographic studies of SAgs have shown that these molecules have similar three-dimensional structures (2, 7). The toxins have a short N-terminal ␣ helix that leads into a  barrel structure known as the B domain or oligosaccharide-binding (O/B) fold. The O/B fold is connected to a C-terminal wall of  strands by a central diagonal ␣ helix, forming domain A ( grasp fold). All SAgs have these features, but some differ slightly in that they have small additional loops. The most notable of these is a cysteine loop structure present in many of the SEs and streptococcal pyrogenic exotoxin A (SPE A). This loop is thought to be important for emetic activity in SEs (4). Recently, SEs I, K, and Q, which lack the cysteine loop structure, have been identified; these toxins were shown to be superantigenic, but the emetic activity was significantly reduced in magnitude (SEI) or lacking (SEK and SEQ) (8-10). In addition, TSST-1, which lacks cysteine residues, was shown to be nonemetic (14).This study was undertaken to purify and characterize a new toxin, designated SEL, whose coding sequence had been detected as an open reading frame in a pathogenicity island (SaPIbov) from a bovine mastitis S. aureus isolate.The gene sel was cloned from S. aureus TSS isolate MN Don. PCR primers were chosen based on the sequences of SaPIbov and SaPI4 (3). PCR primers including several hundred nucleotides at either end of sel were included in the original clone. The PCR product was electrophoresed in 1% agarose, purified, and cloned into the TA vector pGEM T-easy (Promega, Madison, Wis.), resulting in the plasmid pPMO031. This plasmid was transformed into Escherichia coli XL-1 Blue. The entire sequence of sel was determined by automated sequencing (Biomedical Genomics and Advanced Genetic Analysis Centers, University of Minnesota). To examine the biochemical and biological properties of SEL, a sel signal seque...
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