title: Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis.
abstract: BACKGROUND
  Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s) involved in the type shift.
  
  
  RESULTS
  Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5' untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion.
  
  
  CONCLUSIONS
  The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis.
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Han
authors.forename: Asaomi
authors.initials: A
authors.lastname: Kuwae
authors.forename: Akio
authors.initials: A
authors.lastname: Abe
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kamachi
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001886:Bordetella pertussis / Q000235:genetics* / Q000276:immunology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010567:Pertussis Vaccine / Q000276:immunology; D020161:Physical Chromosome Mapping; D011401:Promoter Regions, Genetic / Q000235:genetics; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D001426:Bacterial Proteins; D010567:Pertussis Vaccine; D012333:RNA, Messenger