Pertactin-Deficient Bordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Longhuan Ma; Amanda Caulfield; Kalyan K. Dewan; Eric T. Harvill

Disclosures

Emerging Infectious Diseases. 2021;27(6):1561-1566. 

In This Article

Role of PRN

PRN is an autotransporter protein located on the surface of B. pertussis.[17] Similar to all autotransporters found in gram-negative pathogens, PRN has 3 functional domains: the N terminal signal sequence, the passenger domain, and a C-terminal autotransporter domain. The signal sequence guides the passenger and transporter domains into the periplasm, enabling the transporter domain to form a pore in the outer membrane for translocation of the passenger domain to the cell surface. The protein is then cleaved by an outer membrane protease, the passenger domain remaining in contact with the surface by noncovalent interactions.[18,19]

The function of PRN is only partially understood. PRN is considered one of several virulence factors found in B. pertussis and has been shown to serve as an adhesin, facilitating attachment to various mammalian epithelial cells.[20,21] The 3-dimensional structure of PRN (PDB no. 1DAB) shows 16 right-handed parallel β-helixes, the largest β-helix structure recorded to date. Two Arg–Gly–Asp tripeptide motifs within the helical structure appear to be potential attachment sites to many mammalian adhesion proteins.[22–24] PRN is reported to be essential for resisting neutrophil-mediated clearance and possesses additional immunomodulatory abilities that aid B. pertussis in suppressing the production of proinflammatory cytokines.[25,26] The benefits of functional expression of PRN in pathogenesis are consistent with its conservation in B. pertussis and other pathogenic Bordetella species. Loss of such a factor would be expected to be costly to the organism, yet PRN-deficient strains appear to be rapidly expanding in aP vaccinated populations, suggesting a recent rebalancing of fitness costs and benefits.

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