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Patrick M. Schlievert - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Staphylococcal Toxic Shock Syndrome Toxin 1
    2016
    Co-Authors: On Aortic Endothelial Cells, Peter K. Lee, Gregory M. Vercellotti, James R. Deringer, Patrick M. Schlievert
    Abstract:

    In staphylococcal toxic shock syndrome, hypotension and shock due to capillary leak may rapidly lead to death of the host. To investigate its pathogenesis, the cytotoxic effects of toxic shock syndrome Toxin 1 (TSST-1) on porcine aortic endothelial cells (PAEC) were examined in vitro. TSST-l killed PAEC (as measured by S1Cr release) in a dose- and time-dependent fashion and was blocked by anti-TSST-1 antibodies. Receptor-mediated endocytosis may be critical for the cytotoxic effects of TSST-1, as killing was inhibited by cold (4°C) and by addition of chloro-quine and methylamine. Furthermore, calcium and oxygen appeared necessary for TSST-1 ef-fects on PAEC. Membrane receptor binding studies indicated PAEC bind TSST-1 with high affinity (Kd = 5.7 X 10-7 M) and had 2.2 X 104 receptors/cell. Last, as measured by 12sI-labeled albumin flux in a transendothelial permeability model, TSST-1 enhanced the permeability of PAEC monolayers in a dose- and time-dependent manner. Toxic shock syndrome (TSS) is an acute multisystem ill-ness characterized by the sudden onset offever, hypotension, rash, variable multiorgan involvement, and desquamation of the skin on recovery [1-3]. Since its first description in 197

  • novel toxic shock syndrome Toxin 1 amino acids required for biological activity
    Biochemistry, 2008
    Co-Authors: Amanda J. Brosnahan, Christopher A Squier, Mary J. Mantz, Marnie L. Peterson, Matthew M Schaefers, William H Amundson, Patrick M. Schlievert
    Abstract:

    Superantigens interact with T lymphocytes and macrophages to cause T lymphocyte proliferation and overwhelming cytokine production, which lead to toxic shock syndrome. Staphylococcus aureus superantigen toxic shock syndrome Toxin-1 is a major cause of menstrual toxic shock syndrome. In general, superantigen-secreting S. aureus remains localized at the vaginal surface, and the superantigen must therefore penetrate the vaginal mucosa to interact with underlying immune cells to cause toxic shock syndrome. A dodecapeptide region (toxic shock syndrome Toxin-1 amino acids F119-D130), relatively conserved among superantigens, has been implicated in superantigen penetration of the epithelium. The purpose of this study was to determine amino acids within this dodecapeptide region that are required for interaction with vaginal epithelium. Alanine mutations were constructed in S. aureus toxic shock syndrome Toxin-1 amino acids D120 to D130. All mutants maintained superantigenicity, and selected mutants were lethal when given intravenously to rabbits. Toxic shock syndrome Toxin-1 induces interleukin-8 from immortalized human vaginal epithelial cells; however, three Toxin mutants (S127A, T128A, and D130A) induced low levels of interleukin-8 compared to wild type Toxin. When carboxy-terminal mutants (S127A to D130A) were administered vaginally to rabbits, D130A was nonlethal, while S127A and T128A demonstrated delayed lethality compared to wild type Toxin. In a porcine ex vivo permeability model, mutant D130A penetrated the vaginal mucosa more quickly than wild type Toxin. Toxic shock syndrome Toxin-1 residue D130 may contribute to binding an epithelial receptor, which allows it to penetrate the vaginal mucosa, induce interleukin-8, and cause toxic shock syndrome.

  • penetration of toxic shock syndrome Toxin 1 across porcine vaginal mucosa ex vivo permeability characteristics Toxin distribution and tissue damage
    American Journal of Obstetrics and Gynecology, 2003
    Co-Authors: Catherine C Davis, Patrick M. Schlievert, Mary Kremer, Christopher A Squier
    Abstract:

    Abstract Objective The purpose of this study was to evaluate transvaginal penetration of toxic shock syndrome Toxin-1 and its effects on permeability and tissue integrity in vitro with the use of excised porcine vaginal mucosa. Study design Permeability to tritiated water (1 and 10 μg/mL applied Toxin) and transmucosal flux of 35 S-methionine-labeled toxic shock syndrome Toxin-1 (10 and 20 μg/mL) for up to 12 hours were assessed with the use of a continuous flow perfusion system. The location of labeled Toxin that penetrated the mucosal tissue strata was determined. The integrity of Toxin-treated, intact, scalpel-incised tissue was evaluated histopathologically. Results Toxic shock syndrome Toxin-1 caused a non-dose-dependent increase in mucosal permeability and traversed the intact mucosa at a low rate without disrupting tissue integrity. In incised vaginal mucosa, toxic shock syndrome Toxin-1 induced subepithelial separation and atrophy that were analogous to clinically relevant vaginal lesions that were reported in fatal cases of menstrual toxic shock syndrome. Conclusion An in vitro model could be used to demonstrate that toxic shock syndrome Toxin-1 permeates the vaginal mucosa and distributes throughout the tissue. Histologic evaluation of tissues that were exposed to toxic shock syndrome Toxin-1 demonstrated lesions that were similar to those lesions that were reported in cases of menstrual toxic shock syndrome.

  • toxic shock syndrome Toxin secreting staphylococcus aureus in kawasaki syndrome
    The Lancet, 1993
    Co-Authors: D Y M Leung, B L Kotzin, H C Meissner, R D Fulton, Debra L Murray, Patrick M. Schlievert
    Abstract:

    Kawasaki syndrome (KS), the main cause of acquired heart disease in children, is associated with the selective expansion of V beta 2+ T cells in peripheral blood. Our study suggests that KS may be caused by a superantigen--a staphylococcal or streptococcal Toxin. Bacteria were cultured without knowledge of their origin, from the throat, rectum, axilla, and groin of 16 patients with untreated acute KS and 15 controls. Bacteria producing Toxins were isolated from 13 of 16 KS patients but from only 1 of 15 controls (p < 0.0001). Toxic shock syndrome Toxin (TSST) secreting Staphylococcus aureus was isolated from 11 of the 13 Toxin-positive cultures, and streptococcal pyogenic exoToxin (SPE) B and C were found in the other 2. These Toxins are known to stimulate V beta 2+ T cells. All TSST-producing KS isolates were tryptophan auxotrophs indicating they were clonally related. S aureus isolates from acute KS patients were unusual because they produced less lipase, haemolysin, and protease compared to other isolates (p < 0.01). S aureus colonies from KS patients were white, and could be easily mistaken for coagulase-negative staphylococci, whereas colonies of non-KS isolates were gold. These observations suggest that the expansion of V beta 2+ T cells in most patients with KS may be caused by a new clone of TSST-producing S aureus, and, in a minority of patients, SPEB-producing or SPEC-producing streptococci.

  • toxic shock syndrome Toxin secreting staphylococcus aureus in kawasaki syndrome
    The Lancet, 1993
    Co-Authors: D Y M Leung, B L Kotzin, H C Meissner, R D Fulton, Debra L Murray, Patrick M. Schlievert
    Abstract:

    Abstract Summary Kawasaki syndrome (KS), the main cause of acquired heart disease in children, is associated with the selective expansion of Vβ2 + T cells in peripheral blood. Our study suggests that KS may be caused by a superantigen—a staphylococcal or streptococcal Toxin. Bacteria were cultured without knowledge of their origin, from the throat, rectum, axilla, and groin of 16 patients with untreated acute KS and 15 controls. Bacteria producing Toxins were isolated from 13 of 16 KS patients but from only 1 of 15 controls (p These observations suggest that the expansion of Vβ2 + T cells in most patients with KS may be caused by a new clone of TSST-producing S aureus, and, in a minority of patients, SPEB-producing or SPEC-producing streptococci.

Christopher A Squier - One of the best experts on this subject based on the ideXlab platform.

  • novel toxic shock syndrome Toxin 1 amino acids required for biological activity
    Biochemistry, 2008
    Co-Authors: Amanda J. Brosnahan, Christopher A Squier, Mary J. Mantz, Marnie L. Peterson, Matthew M Schaefers, William H Amundson, Patrick M. Schlievert
    Abstract:

    Superantigens interact with T lymphocytes and macrophages to cause T lymphocyte proliferation and overwhelming cytokine production, which lead to toxic shock syndrome. Staphylococcus aureus superantigen toxic shock syndrome Toxin-1 is a major cause of menstrual toxic shock syndrome. In general, superantigen-secreting S. aureus remains localized at the vaginal surface, and the superantigen must therefore penetrate the vaginal mucosa to interact with underlying immune cells to cause toxic shock syndrome. A dodecapeptide region (toxic shock syndrome Toxin-1 amino acids F119-D130), relatively conserved among superantigens, has been implicated in superantigen penetration of the epithelium. The purpose of this study was to determine amino acids within this dodecapeptide region that are required for interaction with vaginal epithelium. Alanine mutations were constructed in S. aureus toxic shock syndrome Toxin-1 amino acids D120 to D130. All mutants maintained superantigenicity, and selected mutants were lethal when given intravenously to rabbits. Toxic shock syndrome Toxin-1 induces interleukin-8 from immortalized human vaginal epithelial cells; however, three Toxin mutants (S127A, T128A, and D130A) induced low levels of interleukin-8 compared to wild type Toxin. When carboxy-terminal mutants (S127A to D130A) were administered vaginally to rabbits, D130A was nonlethal, while S127A and T128A demonstrated delayed lethality compared to wild type Toxin. In a porcine ex vivo permeability model, mutant D130A penetrated the vaginal mucosa more quickly than wild type Toxin. Toxic shock syndrome Toxin-1 residue D130 may contribute to binding an epithelial receptor, which allows it to penetrate the vaginal mucosa, induce interleukin-8, and cause toxic shock syndrome.

  • penetration of toxic shock syndrome Toxin 1 across porcine vaginal mucosa ex vivo permeability characteristics Toxin distribution and tissue damage
    American Journal of Obstetrics and Gynecology, 2003
    Co-Authors: Catherine C Davis, Patrick M. Schlievert, Mary Kremer, Christopher A Squier
    Abstract:

    Abstract Objective The purpose of this study was to evaluate transvaginal penetration of toxic shock syndrome Toxin-1 and its effects on permeability and tissue integrity in vitro with the use of excised porcine vaginal mucosa. Study design Permeability to tritiated water (1 and 10 μg/mL applied Toxin) and transmucosal flux of 35 S-methionine-labeled toxic shock syndrome Toxin-1 (10 and 20 μg/mL) for up to 12 hours were assessed with the use of a continuous flow perfusion system. The location of labeled Toxin that penetrated the mucosal tissue strata was determined. The integrity of Toxin-treated, intact, scalpel-incised tissue was evaluated histopathologically. Results Toxic shock syndrome Toxin-1 caused a non-dose-dependent increase in mucosal permeability and traversed the intact mucosa at a low rate without disrupting tissue integrity. In incised vaginal mucosa, toxic shock syndrome Toxin-1 induced subepithelial separation and atrophy that were analogous to clinically relevant vaginal lesions that were reported in fatal cases of menstrual toxic shock syndrome. Conclusion An in vitro model could be used to demonstrate that toxic shock syndrome Toxin-1 permeates the vaginal mucosa and distributes throughout the tissue. Histologic evaluation of tissues that were exposed to toxic shock syndrome Toxin-1 demonstrated lesions that were similar to those lesions that were reported in cases of menstrual toxic shock syndrome.

Wendy M Johnson - One of the best experts on this subject based on the ideXlab platform.

  • multiplex pcr for detection of genes for staphylococcus aureus enteroToxins exfoliative Toxins toxic shock syndrome Toxin 1 and methicillin resistance
    Journal of Clinical Microbiology, 2000
    Co-Authors: Manisha Mehrotra, Gehua Wang, Wendy M Johnson
    Abstract:

    A multiplex PCR assay for detection of genes for staphylococcal enteroToxins A to E (entA, entB, entC, entD, and entE), toxic shock syndrome Toxin 1 (tst), exfoliative Toxins A and B (etaA and etaB), and intrinsic methicillin resistance (mecA) was developed. Detection of femA was used as an internal positive control. The multiplex PCR assay combined the primers for sea to see and femA in one set and those for eta, etb, tst, mecA, and femA in the other set. Validation of the assay was performed using 176 human isolates of Staphylococcus aureus. This assay offers a very specific, quick, reliable, and inexpensive alternative to conventional PCR assays used in clinical laboratories to identify various staphylococcal Toxin genes.

  • detection of genes for enteroToxins exfoliative Toxins and toxic shock syndrome Toxin 1 in staphylococcus aureus by the polymerase chain reaction
    Journal of Clinical Microbiology, 1991
    Co-Authors: Wendy M Johnson, Shaun Tyler, E P Ewan, F E Ashton, D R Pollard, K R Rozee
    Abstract:

    Eight pairs of synthetic oligonucleotide primers were used in a polymerase chain reaction (PCR) protocol to detect genes for staphylococcal enteroToxins A to E, exfoliative Toxins A and B, and toxic shock syndrome Toxin 1 in Staphylococcus aureus strains isolated from clinical specimens and contaminated foods. Primers were targeted to internal regions of the Toxin genes, and amplification fragments were detected after the PCR by agarose gel electrophoresis. Unequivocal discrimination of Toxin genes was obtained by the PCR by using nucleic acids extracted from 88 strains of S. aureus whose toxigenicity was established biologically and immunologically. In immunological assays, two strains of S. aureus produced equivocal results for production of enteroToxin C or toxic shock syndrome Toxin 1, giving an overall concordance between phenotypic and genotypic identification of 97.7%. Primer specificity was established in the PCR by using nucleic acids from known Toxin-producing bacterial pathogens and from nontoxigenic S. aureus. Strains of Streptococcus spp., including some producers of pyrogenic exoToxin A carrying the speA gene, were negative by the PCR designed to detect staphylococcal Toxins. The detection limits were established for all the staphylococcal Toxin genes within their respective PCR protocols. The identification of staphylococcal Toxin genes in strains of S. aureus by the PCR offers a very specific, sensitive, relatively rapid, and inexpensive alternative to traditional immunological assays which depend on adequate gene expression for reliability and sensitivity. Images

Takashi Tsuge - One of the best experts on this subject based on the ideXlab platform.

  • dissection of the host range of the fungal plant pathogen alternaria alternata by modification of secondary metabolism
    Molecular Microbiology, 2004
    Co-Authors: Takayoshi Tanaka, Rieko Hatta, Mikihiro Yamamoto, Kazuya Akimitsu, Takashi Tsuge
    Abstract:

    Summary The filamentous fungus Alternaria alternata contains seven pathogenic variants (pathotypes), which produce different host-specific Toxins and cause diseases on different plants. The strawberry pathotype produces host-specific AF-Toxin and causes Alternaria black spot of strawberry. This pathotype is also pathogenic to Japanese pear cultivars susceptible to the Japanese pear pathotype that produces AK-Toxin. The strawberry pathotype produces two related molecular species, AF-Toxins I and II: Toxin I is toxic to both strawberry and pear, and Toxin II is toxic only to pear. Previously, we isolated a cosmid clone pcAFT-1 from the strawberry pathotype that contains three genes involved in AF-Toxin biosynthesis. Here, we have identified a new gene, designated AFTS1, from pcAFT-1. AFTS1 encodes a protein with similarity to enzymes of the aldo-ketoreductase superfamily. Targeted mutation of AFTS1 diminished the host range of the strawberry pathotype: ΔaftS1 mutants were pathogenic to pear, but not to strawberry, as is the Japanese pear pathotype. These mutants were found to produce AF-Toxin II, but not AF-Toxin I. These data represent a novel example of how the host range of a plant pathogenic fungus can be restricted by modification of secondary metabolism.

  • dissection of the host range of the fungal plant pathogen alternaria alternata by modification of secondary metabolism
    Molecular Microbiology, 2004
    Co-Authors: Kaoru Ito, Rieko Hatta, Takayoshi Tanaka, Mikihiro Yamamoto, Kazuya Akimitsu, Takashi Tsuge
    Abstract:

    The filamentous fungus Alternaria alternata contains seven pathogenic variants (pathotypes), which produce different host-specific Toxins and cause diseases on different plants. The strawberry pathotype produces host-specific AF-Toxin and causes Alternaria black spot of strawberry. This pathotype is also pathogenic to Japanese pear cultivars susceptible to the Japanese pear pathotype that produces AK-Toxin. The strawberry pathotype produces two related molecular species, AF-Toxins I and II: Toxin I is toxic to both strawberry and pear, and Toxin II is toxic only to pear. Previously, we isolated a cosmid clone pcAFT-1 from the strawberry pathotype that contains three genes involved in AF-Toxin biosynthesis. Here, we have identified a new gene, designated AFTS1, from pcAFT-1. AFTS1 encodes a protein with similarity to enzymes of the aldo-ketoreductase superfamily. Targeted mutation of AFTS1 diminished the host range of the strawberry pathotype: Delta aftS1 mutants were pathogenic to pear, but not to strawberry, as is the Japanese pear pathotype. These mutants were found to produce AF-Toxin II, but not AF-Toxin I. These data represent a novel example of how the host range of a plant pathogenic fungus can be restricted by modification of secondary metabolism.

Jeffrey L C Wright - One of the best experts on this subject based on the ideXlab platform.

  • sulfated diesters of okadaic acid and dtx 1 self protective precursors of diarrhetic shellfish poisoning dsp Toxins
    Harmful Algae, 2017
    Co-Authors: Patricia Leblanc, Pearse Mccarron, Jeffrey L C Wright, Ian W Burton, John A Walter, Jeremy E Melanson, Wendy K Strangman
    Abstract:

    Many toxic secondary metabolites used for defense are also toxic to the producing organism. One important way to circumvent toxicity is to store the Toxin as an inactive precursor. Several sulfated diesters of the diarrhetic shellfish poisoning (DSP) Toxin okadaic acid have been reported from cultures of various dinoflagellate species belonging to the genus Prorocentrum. It has been proposed that these sulfated diesters are a means of Toxin storage within the dinoflagellate cell, and that a putative enzyme mediated two-step hydrolysis of sulfated diesters such as DTX-4 and DTX-5 initially leads to the formation of diol esters and ultimately to the release of free okadaic acid. However, only one diol ester and no sulfated diesters of DTX-1, a closely related DSP Toxin, have been isolated leading some to speculate that this Toxin is not stored as a sulfated diester and is processed by some other means. DSP components in organic extracts of two large scale Prorocentrum lima laboratory cultures have been investigated. In addition to the usual suite of okadaic acid esters, as well as the free acids okadaic acid and DTX-1, a group of corresponding diol- and sulfated diesters of both okadaic acid and DTX-1 have now been isolated and structurally characterized, confirming that both okadaic acid and DTX-1 are initially formed in the dinoflagellate cell as the non-toxic sulfated diesters.