Genome-Wide Gene Expression Analysis of Bordetella pertussis Isolates Associated with a Resurgence in Pertussis: Elucidation of Factors Involved in the Increased Fitness of Epidemic Strains

Abstract

Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. Despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. A recent resurgence pertussis is associated with the expansion of B. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxP3 in place of resident ptxP1 strains. The recent expansion of ptxP3 strains suggests that these strains carry mutations that have increased their fitness. Compared to the ptxP1 strains, ptxP3 strains produce more Ptx, which results in increased virulence and immune suppression. In this study, we investigated the contribution of gene expression changes of various genes on the increased fitness of the ptxP3 strains. Using genome-wide gene expression profiling, we show that several virulence genes had higher expression levels in the ptxP3 strains compared to the ptxP1 strains. We provide the first evidence that wildtype ptxP3 strains are better colonizers in an intranasal mouse infection model. This study shows that the ptxP3 mutation and the genetic background of ptxP3 strains affect fitness by contributing to the ability to colonize in a mouse infection model. These results show that the genetic background of ptxP3 strains with a higher expression of virulence genes contribute to increased fitness.

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

“…Surprisingly, the SNP cluster I strain also outcompeted the SNP cluster II strain in the naïve host environment, suggesting that the SNP cluster I strain has evolved to achieve better fitness regardless of the host environment. Our findings are supported by a previous report by King et al [20] which compared the colonisation difference between Dutch pxtP3 and ptxP1 strains which were equivalent to our SNP cluster I and SNP cluster II strains, respectively. They also found better colonisation of wild-type ptxP3 strains in the lungs and trachea of naïve mice when assessed at day 4 of the infection [20].…”

“…Our findings are supported by a previous report by King et al [20] which compared the colonisation difference between Dutch pxtP3 and ptxP1 strains which were equivalent to our SNP cluster I and SNP cluster II strains, respectively. They also found better colonisation of wild-type ptxP3 strains in the lungs and trachea of naïve mice when assessed at day 4 of the infection [20]. Furthermore, they found that the advantage of ptxP3 strains also depended on their genetic background [20].…”

“…They also found better colonisation of wild-type ptxP3 strains in the lungs and trachea of naïve mice when assessed at day 4 of the infection [20]. Furthermore, they found that the advantage of ptxP3 strains also depended on their genetic background [20]. Therefore, this line of evidence suggests that the increased fitness cannot be explained by the simple advantage provided by the ptxP3 allele resulting in increased Ptx production [21].…”

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

“…Although the ptxP3 allele is thought to increase pertussis toxin expression (40,41), a recent comparison of isogenic mutants found that the ptxP3 allele and the genetic background, which includes genomic structure, independently enhance colonization in mice (42). Similarly, although alleles of fimH contain polymorphisms in the predicted surface epitope region, differences in immune recognition remain untested (43).…”

Whole-cell pertussis vaccine potency assays: the Kendrick test and alternative assays

“…With the observed increase of pertussis in various vaccinating countries in recent years, antigenic mutations were reported in circulating B. pertussis strains [61][62][63][64]. Global transmission of new strains is very rapid and the worldwide population of B. pertussis is evolving in response to vaccine introduction [65].…”