title: Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani.
abstract: Botulinum and tetanus neurotoxins are structurally and functionally related proteins that are potent inhibitors of neuroexocytosis. Botulinum neurotoxin (BoNT) associates with non-toxic proteins (ANTPs) to form complexes of various sizes, whereas tetanus toxin (TeNT) does not form any complex. The BoNT and ANTP genes are clustered in a DNA segment called the botulinum locus, which has different genomic localization (chromosome, plasmid, phage) in the various Clostridium botulinum types and subtypes. The botulinum locus genes are organized in two polycistronic operons (ntnh-bont and ha/orfX operons) transcribed in opposite orientations. A gene called botR lying between the two operons in C. botulinum type A encodes an alternative sigma factor which regulates positively the synthesis of BoNT and ANTPs at the late exponential growth phase and beginning of the stationary phase. In Clostridium tetani, the gene located immediately upstream of tent encodes a positive regulatory protein, TetR, which is related to BotR. C. botulinum and C. tetani genomes contain several two-component systems and predicted regulatory orphan genes. In C. botulinum type A, four two-component systems have been found that positively or negatively regulate the synthesis of BoNT and ANTPs independently of BotR/A. The synthesis of neurotoxin in Clostridia seems to be under the control of complex network of regulation.
authors.affiliation: Institut Pasteur, Unité des Bactéries Anaérobies et Toxine, 25 rue du Dr Rouxs, Paris cedex15, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Connan
authors.forename: Cécile
authors.initials: C
authors.lastname: Denève
authors.forename: Christelle
authors.initials: C
authors.lastname: Mazuet
authors.forename: Michel R
authors.initials: MR
authors.lastname: Popoff
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001905:Botulinum Toxins / Q000096:biosynthesis* / Q000235:genetics; D003014:Clostridium botulinum / Q000235:genetics* / Q000378:metabolism; D003017:Clostridium tetani / Q000235:genetics* / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D056426:Genetic Loci; D009876:Operon / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D053038:Quorum Sensing / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D013744:Tetanus Toxin / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C116103:BotR protein, Clostridium botulinum; D004269:DNA, Bacterial; D012808:Sigma Factor; C116102:TetR protein, Clostridium tetani; D013744:Tetanus Toxin; D015534:Trans-Activators; D001905:Botulinum Toxins
keywords: Botulinum neurotoxin; Clostridium botulinum; Clostridium tetani; Regulation; Tetanus toxin