Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies

Abstract

Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines.

FIG. 1.

Phylogenetic relationships among the nine known Bordetella species based on a combination of multilocus enzyme electrophoresis, IS element, and sequence analysis. These species appear to have descended from a common B. petrii ancestor. Further, B. bronchiseptica appears to be the evolutionary progenitor of B. pertussis, B. parapertussis_hu, and B. parapertussis_ov; as such, these species have been reclassified as subspecies of the “B. bronchiseptica cluster.”

FIG. 2.

(A) The BvgAS phosphorelay. BvgS is a transmembrane sensor protein consisting of a periplasmic domain (P), a linker region (L), and histidine kinase (HPK), receiver (R), and histidine phosphotransfer domains (HPD). BvgA is a response regulator that contains receiver (R) and helix-turn-helix (HTH) domains. Under inducing signals, BvgS autophosphorylates and initiates a phosphorelay that eventually leads to the phosphorylation and activation of BvgA. The sequential steps in the phosphorelay and the amino acid residues involved are shown. The bvgS-C3 allele confers constitutive activity. BvgAS controls as least three distinct phenotypic phases in response to environmental conditions. The Bvg⁺ phase or X mode is necessary and sufficient for respiratory tract colonization and is associated with the expression of virulence factors. The Bvgⁱ phase is hypothesized to be important for respiratory transmission and is characterized by the expression of a subset of Bvg⁺ phase-specific factors as well as factors expressed maximally in the Bvgⁱ phase. B. pertussis and B. bronchiseptica express a significantly different array of proteins in their Bvg⁻ phase. The Bvg⁻ phase of B. bronchiseptica is necessary and sufficient for growth under nutrient-limiting conditions and is predicted to play a role in survival in the environment. Other abbreviations: om, outer membrane; cm, cell membrane. (B) Expression curves for the four classes of genes regulated by BvgAS. Genes expressed maximally in the Bvg⁺ phase (such as cyaA) are referred to as “late” Bvg-activated genes and are represented by the black curve (curve 1). Genes that are expressed maximally under both Bvg⁺ and Bvgⁱ phase conditions (such as fhaB) are referred to as “early” Bvg-activated genes and are represented by the green curve (curve 2). Genes expressed maximally only under Bvgⁱ phase conditions (such as bipA) are represented by the gold curve (curve 3). Finally, genes that are repressed by BvgAS and expressed maximally only under Bvg⁻ phase conditions are represented by the red curve (curve 4). Abbreviation: nic, nicotinic acid.

FIG. 3.

Number of cases of pertussis in the United States from 1940 to 2002 (http://www.cdc.gov/nip/ed/slides/pertussis8p.ppt).

FIG. 4.

Number of cases of pertussis in the United States from 1980 to 2002 (http://www.cdc.gov/nip/ed/slides/pertussis8p.ppt).

FIG. 5.

Age distribution and incidence of reported cases of pertussis in the United States from 1997 to 2000 (http://www.cdc.gov/nip/ed/slides/pertussis8p.ppt).