title: Localization of superantigen virulence factors in kidney tissue of animals with Staphylococcus aureus-infected burn wounds.
abstract: Gram-positive organisms are often found in association with burn wounds. A paucity of information exists regarding the accumulation and fate of virulence factors from these bacteria. The superantigenic exotoxins produced by Staphylococcus aureus are potent immunomodulating proteins and have also been described to localize in the kidney. The aim of this work was to demonstrate renal accumulation of toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin B (SEB) in a methicillin-resistant S. aureus burn wound infection. Twelve Sprague Dawley rats were subjected to partial-thickness burns (2 × 2 cm) using an aluminum billet. On postburn day 1, the wounds were inoculated with a toxin-producing strain of methicillin-resistant  Skin biopsies and serum were obtained on postburn days 3, 6, and 10 along with necropsies for three animals each day. An enzyme-linked immunosorbent assay was used to quantify amounts of TSST-1 and SEB. Immunohistochemistry was used to localize SEB, TSST-1, and cleaved caspase-3 in renal tissue, and quantitative real-time polymerase chain reaction was used to assess erythropoietin and endothelin-1 messenger RNA (mRNA) in renal tissue. Baseline skin and plasma levels of TSST-1 and SEB were not detectable. Skin biopsy TSST-1 levels were detected on all postburn days and peaked at a mean value of 39.35 ng/ml on day 6; SEB was found in the skin and kidney only on postburn days 6 and 10. An enzyme-linked immunosorbent assay of renal tissue for TSST-1 and SEB demonstrated significantly higher (P < .05) mean toxin concentrations on postburn day 10: 10.87 ng/ml for TSST-1 and 0.67 ng/ml for SEB. Immunohistochemistry of renal tissue demonstrated increased stain intensity for SEB, TSST-1, and cleaved caspase-3 over time. Quantitative real-time polymerase chain reaction demonstrated decreased expression erythropoietin mRNA and increased expression of endothelin-1 mRNA relative to negative controls (P < .01). In a burn wound infection model that is nonlethal and lacks bacteremia, TSST-1 and SEB traverse cutaneous wounds and localize to the kidney. These potent virulence factors may contribute to the induction of apoptosis, and may alter homeostasis via renal pathophysiology.
authors.affiliation: Department of Surgery, Burn Center, MedStar Washington Hospital Center, MedStar Health Research Institute, Washington, District of Columbia 20010, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Mino
authors.forename: Rachel T
authors.initials: RT
authors.lastname: Ortiz
authors.forename: Pranay
authors.initials: P
authors.lastname: Randad
authors.forename: Lauren T
authors.initials: LT
authors.lastname: Moffatt
authors.forename: Marion H
authors.initials: MH
authors.lastname: Jordan
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Shupp
mesh_terms: D000818:Animals; D001706:Biopsy; D002056:Burns / Q000276:immunology* / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus; D018089:Superantigens / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*; D014946:Wound Infection / Q000382:microbiology*
chemical_list: D018089:Superantigens; D037521:Virulence Factors