studies on prn variation in the mouse model and comparison with epidemiological data研究对变异的小鼠模型和比较流行病学数据.pdf

Studies on Prn Variation in the Mouse Model and Comparison with Epidemiological Data 1. 2. 1 1 3 Marjolein van Gent , Inge H. M. van Loo , Kees J. Heuvelman , Albert J. de Neeling , Peter Teunis , Frits R. Mooi1* 1 Laboratory for Infectious Diseases and Screening, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands, 2 Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands, 3 Expertise Centre for Methodology and Information Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands Abstract The virulence factor pertactin (Prn) is a component of pertussis vaccines and one of the most polymorphic Bordetella pertussis antigens. After the introduction of vaccination shifts in predominant Prn types were observed and strains with the Prn vaccine type (Prn1) were replaced by strains carrying non-vaccine types (Prn2 and Prn3), suggesting vaccine-driven selection. The aim of this study was to elucidate the shifts observed in Prn variants. We show that, although Prn2 and Prn3 circulated in similar frequencies in the 1970s and 1980s, in the 1990s Prn2 strains expanded and Prn3 strains disappeared, suggesting that in vaccinated populations Prn2 strains are fitter than Prn3 strains. We established a role for Prn in the mouse model by showing that a Prn knock-out (Prn-ko) mutation reduced colonization in trachea and lungs. Restoration of the mutation resulted in a significant increase in colonization compared to the knock-out mutant. The ability of clinical isolates with different Prn variants to colonize the mou