title: Role of the Flagellar Hook-Length Control Protein FliK and σ28 in cagA Expression in Gastric Cell-Adhered Helicobacter pylori.
abstract: Adherence of Helicobacter pylori to the gastric epithelial cell line AGS strongly induces expression of fliK encoding a flagellar hook-length control protein. FliK has a role in triggering dissociation of the alternate sigma factor, σ(28), from a nonfunctional σ(28)-FlgM complex, releasing free, functional σ(28). The σ(28)-RNA polymerase initiates transcription of cagA, the major virulence gene, from a promoter identified in this study. Consequently, significant up-regulation of cagA was observed in AGS-adhered H. pylori. Direct binding of σ(28) to the cagA promoter was demonstrated by chromatin immunoprecipitation and the transcription start site was identified by 5' RACE (rapid amplification of complementary DNA ends). The σ(28)-dependent cagA promoter was active specifically in AGS-adhered H. pylori, and this motif might be associated with high cagA expression and severity of disease. These results also indicate that H. pylori has evolved to integrate expression of the major virulence gene cagA with the flagellar regulatory circuit, essential for colonization of the human host.
authors.affiliation: Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Baidya
authors.affiliation: Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Chowdhury
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000166:cytology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C064971:FliA protein, Bacteria; C099486:FliK protein, Bacteria; D012808:Sigma Factor; C080866:cagA protein, Helicobacter pylori
keywords: CagA; FliK; Sigma 28; host-pathogen interaction