Differentially Expressed Genes in Bordetella pertussis Strains Belonging to a Lineage Which Recently Spread Globally

Abstract

Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel vaccine candidates.

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).…”

Bordetella pertussisand pertactin-deficient clinical isolates: lessons for pertussis vaccines

“…Other studies not yet confirmed hypothesized the possible overexpression of virulence factors such as PT or differential gene expression regulation of nonvaccine-type isolates harboring the ptxP3 allele [65]. Genetic expression is however highly dependent on growth conditions such as the medium used, and these results are hard to reproduce.…”

Laboratory Diagnosis of Pertussis

“…This is unfortunate, as strains are required for more in-depth analyses, such as whole-genome sequencing, transcriptomics, and proteomics (44)(45)(46)(47). A convenient way to obtain isolates, without compromising PCR, is to streak a nasopharyngeal swab on selective media after elution of the swab with water or physiological salt for PCR.…”