Studies on Prn variation in the mouse model and comparison with epidemiological data - PubMed (original) (raw)

Comparative Study

Studies on Prn variation in the mouse model and comparison with epidemiological data

Marjolein van Gent et al. PLoS One. 2011.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Variation in pertactin (A) and temporal trends in the frequency of pertactin alleles (B).

The number in the pertactin sequences indicates the amino acid position relative to the N-terminus. The RGD motif implicated in binding to host receptors has been underlined. Repeat motifs are blocked. Dots and dashes indicate sequence identity with Prn1 and gaps, respectively. No strains were available from the period 1960-1964 to determine allele frequencies. Vaccination against pertussis was introduced in 1953.

Figure 2

Figure 2. Role of Prn in colonization of the mouse respiratory tract.

Mice were infected intranasally with the Tohama I strain (wt), a mutant derivative in which the Prn was inactivated (ko), or a back-mutant in which the Prn gene was restored. Three days post-infection, CFUs were determined in trachea and lungs. The experiment was performed twice, and pooled data from both experiments are shown. Error bars and asterisks indicate 95% confidence intervals and significant differences (P<0.01), respectively.

Figure 3

Figure 3. Effect of variation in Prn on colonization of the mouse lung.

Mice were infected with clinical isolates producing Prn1 (N = 15), Prn2 (N = 5) or Prn3 (N = 8). Three days after infection, the number of CFUs in the lung was determined. Error bars and asterisks indicate 95% confidence intervals and significant differences (P<0.05), respectively.

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