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Regulation of exoprotein synthesis by staphylococcal superantigens

Posted on:2004-05-16Degree:Ph.DType:Dissertation
University:New York UniversityCandidate:Vojtov, NikolaFull Text:PDF
GTID:1464390011471086Subject:Biology
Abstract/Summary:
S. aureus is one of the most prevalent causes of hospital-acquired infections and therefore has a potential for a rapid spread in the population in which many patients might be temporarily or permanently immunocompromised.; To cause disease, S. aureus uses an arsenal of proteins of various biochemical and physiological properties. It produces variety of exoproteins including coagulase, staphylokinase, nucleases, lipases, hyaluronidase, proteases, hemolysins, pyrogenic superantigens (such as enterotoxins and toxic shock syndrome toxin), leukocidins, exfoliatins etc.; Typical virulent strains produce and secrete large quantities of the extracellular toxins and enzymes. However, strains causing toxic shock syndrome (TSS) produce low levels of most exoproteins but high levels of the toxic shock-causing superantigen, TSST-1 (Schlievert et al., 1982). These strains cause local infections that are remarkably apurulent though potentially fatal owing to the effects of the superantigen (Bresler, 1983).; The goal of this work was to analyze the apparent difference in exoprotein production between TSST-1 producers and non-producers. In the course of the work, it was shown that TSST-1 downregulates production of other exotoxins in a global fashion and, in addition, it regulates its own levels. It was determined that TSST-1 protein is the effector molecule and that it regulates expression of the target genes at the level of transcription. Structure-function studies revealed that the N-terminal region and a central region were jointly required for the effect. In case of tst autoregulation, promoter fragment of tst corresponding to (+1) to (−45) was shown to be responsive to the regulation, thus narrowing the target region to 46 bp.; Similar results were obtained for seb (enterotoxin B) gene; as in the case of tst, global downregulation of exoproteins was observed as well as autoregulation.; Cross-inhibitory activities of tst and seb were also demonstrated, although the biological significance, if any, is not yet understood.
Keywords/Search Tags:TSST-1, Tst
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