title: A satellite phage-encoded antirepressor induces repressor aggregation and cholera toxin gene transfer.
abstract: CTXphi is a filamentous bacteriophage whose genome encodes cholera toxin, the principal virulence factor of Vibrio cholerae. We have found that the CTXphi-related element RS1 is a satellite phage whose transmission depends upon proteins produced from a CTX prophage (its helper phage). However, unlike other satellite phages and satellite animal viruses, RS1 can aid the CTX prophage as well as exploit it, due to the RS1-encoded protein RstC. RstC, whose function previously was unknown, is an antirepressor that counteracts the activity of the phage repressor RstR. RstC promotes transcription of genes required for phage production and thereby promotes transmission of both RS1 and CTXphi. Antirepression by RstC also induces expression of the cholera toxin genes, ctxAB, and thus may contribute to the virulence of V.cholerae. In vitro, RstC binds directly to RstR, producing unusual, insoluble aggregates containing both proteins. In vivo, RstC and RstR are both found at the cell pole, where they again appear to form stable complexes. The sequestration/inactivation process induced by RstC resembles those induced by mutant polyglutamine-containing proteins implicated in human neurodegenerative disorders.
authors.affiliation: Howard Hughes Medical Institute, Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.forename: Harvey H
authors.initials: HH
authors.lastname: Kimsey
authors.forename: Anne V
authors.initials: AV
authors.lastname: Kane
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D001426:Bacterial Proteins; D002772:Cholera Toxin / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D018014:Gene Transfer Techniques; D006378:Helper Viruses / Q000235:genetics / Q000502:physiology*; D017912:Inovirus / Q000235:genetics / Q000502:physiology*; D009875:Operator Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D012526:Satellite Viruses / Q000235:genetics / Q000502:physiology*; D012995:Solubility; D014158:Transcription, Genetic; D014734:Vibrio cholerae / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014779:Virus Replication / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C107871:RstR protein, Vibrio cholerae; D014764:Viral Proteins; D002772:Cholera Toxin