Biological activity of toxic shock syndrome toxin 1 and a site-directed mutant, H135A, in a lipopolysaccharide-potentiated mouse lethality model.
A recombinant of toxic shock syndrome toxin 1 (TSST-1) which contains a single histidine-to-alanine mutation at residue 135 (H135A) was analyzed for toxicity and vaccine potential in a lipopolysaccharide (LPS)-potentiated mouse lethality model. The 50% lethal dose (LD50) of TSST-1 in BALB/c mice was 47.2 micrograms/kg, but H135A was not lethal when tested at a dose equivalent to 10 LD50s of TSST-1. Levels of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) in serum were, respectively, 10- and 50-fold higher in LPS-potentiated mice injected with 15 LD50s of TSST-1 than in mice given H135A. Mice injected with only TSST-1 did not have elevated levels of TNF or IFN-gamma in serum, while H135A plus LPS or LPS alone elicited identical, yet very low, levels of TNF and IFN-gamma. An enzyme-linked immunosorbent assay of H135A and TSST-1 with anti-TSST-1 serum yielded very similar dose-response curves, which strongly suggests that H135A serologically and conformationally resembles the native toxin. Mice immunized with H135A developed antibodies that recognized TSST-1 in an enzyme-linked immunosorbent assay and afforded protection against a 15-LD50 challenge of TSST-1 plus LPS. The pooled sera of mice immunized with either TSST-1 or H135A also prevented lymphocyte proliferation due to TSST-1.
Stiles
B G
BG
Division of Toxinology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011.
Krakauer
T
T
Bonventre
P F
PF
D000818:Animals; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology / Q000633:toxicity*; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D013329:Structure-Activity Relationship; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D007371:Interferon-gamma