%0 Journal Article %T Prevalence and Genetic Characterization of Pertactin-Deficient Bordetella pertussis in Japan %A Nao Otsuka %A Hyun-Ja Han %A Hiromi Toyoizumi-Ajisaka %A Yukitsugu Nakamura %A Yoshichika Arakawa %A Keigo Shibayama %A Kazunari Kamachi %J PLOS ONE %D 2012 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0031985 %X 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 (prn1¦¤SS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn£¿ isolates, notably those harboring prn1¦¤SS, 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 prn1¦¤SS 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0031985