{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T20:30:07Z","timestamp":1697315407415},"reference-count":47,"publisher":"Microbiology Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,1]]},"abstract":"<jats:p><jats:italic>Neisseria meningitidis<\/jats:italic>, an obligate human pathogen, remains a leading cause of meningitis and fatal sepsis. Meningococci are known to secrete a family of proteins, such as FrpC, with sequence similarity to the repeat-in-toxin (RTX) proteins via the type I secretion system. The meningococcal type I secretion proteins are encoded at two distant genetic loci,<jats:italic>NMB1400<\/jats:italic>(<jats:italic>hlyB<\/jats:italic>) and<jats:italic>NMB1738<\/jats:italic>\/<jats:italic>1737<\/jats:italic>(<jats:italic>hlyD<\/jats:italic>\/<jats:italic>tolC<\/jats:italic>), and are separated from the RTX toxin-like substrates. We have characterized the promoter elements of both<jats:italic>hlyB<\/jats:italic>and<jats:italic>hlyD<\/jats:italic>by primer extension and<jats:italic>lacZ<\/jats:italic>reporter fusions and revealed the growth phase-dependent upregulation of both genes. In addition, we showed that the MisR\/MisS two-component system negatively regulates the expression of<jats:italic>hlyB<\/jats:italic>and<jats:italic>hlyD<\/jats:italic>\/<jats:italic>tolC<\/jats:italic>. Direct binding of MisR to<jats:italic>hlyB<\/jats:italic>and<jats:italic>hlyD<\/jats:italic>promoters was demonstrated by electrophoretic mobility shift assay (EMSA), and DNase I protection assays identified MisR binding sites overlapping the promoter elements. Direct repression of<jats:italic>hlyB<\/jats:italic>transcription by MisR was supported by<jats:italic>in vitro<\/jats:italic>transcription assays. Mutations in the MisR\/S system affected, but did not eliminate, the growth phase-dependent upregulation of<jats:italic>hlyB<\/jats:italic>, suggesting additional regulatory mechanisms. Increased secretion of RTX toxin-like proteins was detected in the cell-free media from<jats:italic>misS<\/jats:italic>mutant cultures, indicating that the amounts of extracellular RTX toxin-like proteins are, in part, controlled by the abundance of the type I secretion apparatus. This is, to our knowledge, the first example of a two-component system mediating secretion of cytotoxin family proteins by controlling expression of the type I secretion proteins.<\/jats:p>","DOI":"10.1099\/mic.0.023945-0","type":"journal-article","created":{"date-parts":[[2009,4,27]],"date-time":"2009-04-27T22:32:56Z","timestamp":1240871576000},"page":"1588-1601","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of the type I protein secretion system by the MisR\/MisS two-component system in Neisseria meningitidis"],"prefix":"10.1099","volume":"155","author":[{"given":"Soma","family":"Sannigrahi","sequence":"first","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, 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