Pertactin is required for Bordetella species to resist neutrophil-mediated clearance

Infect Immun. 2010 Jul;78(7):2901-9. doi: 10.1128/IAI.00188-10. Epub 2010 Apr 26.

Abstract

Pertactin (PRN) is an autotransporter protein produced by all members of the Bordetella bronchiseptica cluster, which includes B. pertussis, B. parapertussis, and B. bronchiseptica. It is a primary component of acellular pertussis vaccines, and anti-PRN antibody titers correlate with protection. In vitro studies have suggested that PRN functions as an adhesin and that an RGD motif located in the center of the passenger domain is important for this function. Two regions of PRN that contain sequence repeats (region 1 [R1] and R2) show polymorphisms among strains and have been implicated in vaccine-driven evolution. We investigated the role of PRN in pathogenesis using B. bronchiseptica and natural-host animal models. A Deltaprn mutant did not differ from wild-type B. bronchiseptica in its ability to adhere to epithelial and macrophage-like cells in vitro or to establish respiratory infection in rats but was cleared much faster than wild-type bacteria in a mouse lung inflammation model. Unlike wild-type B. bronchiseptica, the Deltaprn mutant was unable to cause a lethal infection in SCID-Bg mice, but, like wild-type bacteria, it was lethal for neutropenic mice. These results suggest that PRN plays a critical role in allowing Bordetella to resist neutrophil-mediated clearance. Mutants producing PRN proteins in which the RGD motif was replaced with RGE or in which R1 and R2 were deleted were indistinguishable from wild-type bacteria in all assays, suggesting that these sequences do not contribute to PRN function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Adhesion / genetics
  • Bacterial Adhesion / physiology
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / physiology*
  • Bordetella / genetics
  • Bordetella / pathogenicity*
  • Bordetella Infections / immunology
  • Bordetella Infections / microbiology*
  • Bordetella bronchiseptica / genetics
  • Bordetella bronchiseptica / pathogenicity
  • Epithelium / microbiology
  • Female
  • Lung / immunology
  • Lung / microbiology
  • Macrophages, Alveolar / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Neutropenia / immunology
  • Neutropenia / microbiology
  • Neutrophils / immunology*
  • Neutrophils / physiology
  • Protein Engineering
  • Rats
  • Rats, Wistar
  • Virulence Factors, Bordetella / genetics

Substances

  • Bacterial Outer Membrane Proteins
  • Virulence Factors, Bordetella
  • pertactin