title: Prevalence and genetic characterization of pertactin-deficient Bordetella pertussis in Japan.
abstract: The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn(-)) B. pertussis was observed in Japan. The Prn(-) isolate was first discovered in 1997, and 33 (27%) Prn(-) isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn(-) isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1ΔSS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn(-) isolates, notably those harboring prn1ΔSS, significantly increased since the early 2000s, and Prn(-) isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn(-) isolates belong to MLVA-186, and 6 and 3 Prn(-) isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn(-) clinical strains (harboring prn1ΔSS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn(-) isolates have a higher growth potential than the Prn(+) back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn(-) strains have arisen and that Prn expression is not essential for fitness under these conditions.
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Otsuka
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Han
authors.forename: Hiromi
authors.initials: H
authors.lastname: Toyoizumi-Ajisaka
authors.forename: Yukitsugu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Keigo
authors.initials: K
authors.lastname: Shibayama
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kamachi
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000032:analysis* / Q000235:genetics; D001886:Bordetella pertussis / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D009154:Mutation; D015995:Prevalence; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014612:Vaccines / Q000235:genetics; D037521:Virulence Factors / Q000172:deficiency; D010566:Virulence Factors, Bordetella / Q000032:analysis* / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D014612:Vaccines; D037521:Virulence Factors; D010566:Virulence Factors, Bordetella; C068929:pertactin