Examination of a virulence mutant uncovers the ribosome biogenesis regulatory protein of Toxoplasma gondii.

Several insertional mutants identified in a screen for Toxoplasma gondii that were defective in establishing a chronic infection had a common site of plasmid insertion. This insertion site was determined to be 43 bp upstream of the transcription initiation site of a gene whose predicted product has homology to ribosome biogenesis regulatory protein Rrs1p, an essential protein required for ribosome biogenesis in Saccharomyces cerevisiae. Northern blot analysis of this locus, termed TgRRS1 , showed that in the C3 mutant, the full-length transcript is down-regulated and at least 1 new smaller transcript is present. Restoration of the intact predicted promoter and locus to TgRRS1 insertional mutant strain C3 did not restore brain cyst formation to the levels of the parent strain. Epitope-tagged TgRRS1 was found to localize to the parasite nucleolus, in an area corresponding to the granular component region. TgRRS1 can serve as a marker for the sub-nucleolar granular component region of T. gondii.

Surfactants, aromatic and isoprenoid compounds, and fatty acid biosynthesis inhibitors suppress Staphylococcus aureus production of toxic shock syndrome toxin 1.

Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1.