Studies on Prn Variation in the Mouse Model and Comparison with Epidemiological Data

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 mouse lung was compared. Although these isolates were also polymorphic at other loci, only variation in the promoter for pertussis toxin (ptxP) and Prn were found to contribute significantly to differences in colonization. Analysis of a subset of strains with the same ptxP allele revealed that the ability to colonize mice decreased in the order Prn1>Prn2 and Prn3. Our results are consistent with the predominance of Prn1 strains in unvaccinated populations. Our results show that ability to colonize mice is practically the same for Prn2 and Prn3. Therefore other factors may have contributed to the predominance of Prn2 in vaccinated populations. The mouse model may be useful to assess and predict changes in the B. pertussis population due to vaccination.

Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model

“…Prn has been shown to facilitate adhesion and resistance of B. pertussis to neutrophil-mediated clearance [25,30]. Previous studies have indicated that Prn knockouts were less efficient in colonising the mouse lungs [24]. Our results confirmed these observations.…”

“…A recent study by van Gent et al showed that the prn knock-out mutant had decreased ability to colonise the trachea and lungs in mice, but complementation of the prn knock-out mutant restored this ability [24]. In B. bronchiseptica, Prn also plays a role in resistance to neutrophil-mediated clearance, promoting persistence in the lower respiratory tract [25].…”

Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study

“…Polak et al showed that strains carrying ptxA1/ptxP1/prn2 colonised better than ptxA1/ ptxP1/prn1 or ptxA1/ptxP1/prn3 strains at day 14 post-challenge in mice, suggesting better fitness of strains with prn2 allele [36]. In contrast, van Gent et al showed in naïve mice that the prn1 strain colonised significantly better than prn2 or prn3 strains suggesting better fitness of prn1 strains [37].…”

Prevalence and Genetic Characterization of Pertactin-Deficient Bordetella pertussis in Japan

“…A recent study showed that B. pertussis Prn − mutants colonized less well than Prn + strains in mice [18]. It is also known that Prn prevents either bacterial adherence or internalization or both, to human monocyte-derived dendritic cells [30] and that it also plays a role in resistance to neutrophil-mediated clearance [31].…”