Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model

Kimura, Alan; Mountzouros, K T; Relman, David A.; Falkow, Stanley; Cowell, J L

doi:10.1128/iai.58.1.7-16.1990

Cited by 147 publications

(94 citation statements)

References 37 publications

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“…A lack of this protein did not appear to affect survival deeper in the lungs. This result is similar to that reported by Kimura et al (1990) when they examined an FHA-defective 6. pertussis strain in the mouse aerosol model. When animals were infected with an FHA-defective strain, the numbers of bacteria isolated from the trachea were significantly lower than the number isolated after infection with the wild-type organism.…”

Section: Discussionsupporting

confidence: 91%

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Finn

Stevens

1995

Molecular Microbiology

110

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We report here the identification of a virulence-associated factor, Tcf, (tracheal colonization factor), produced by strains of Bordetella pertussis but not Bordetella parapertussis or Bordetella bronchiseptica. This protein is encoded by the tcfA gene. When a strain of B. pertussis 18323 lacking this protein is used to infect mice with an aerosol challenge, the number of bacteria isolated from the tracheas is decreased 10-fold when compared with the parent 18323. The derived amino acid sequence of tcfA predicts a 68 kDa RGD-containing, proline-rich protein, which after cleavage of a typical prokaryotic signal sequence would be 64 kDa. Amino acid sequence analysis demonstrates that the C-terminal 30 kDa of this protein shows 50% identity to the 30 kDa C-terminus of another Bordetella protein, the pertactin precursor. The N-terminal 34 kDa region contains the three amino-acid motif RGD and is 16.5% proline. Coupled in vitro transcription and translation analysis indicates that the tcfA gene product migrates as two bands of approximately 90 kDa. A fusion protein of the N-terminal, 34 kDa portion of Tcf to maltose-binding protein migrates, on SDS-PAGE, 30 kDa higher than expected from the combined molecular weights. Polyclonal antisera raised against the unique N-terminal portion of Tcf recognizes 90 kDa and 60 kDa bands in immunoblots of whole-cell lysates of strains of B. pertussis; it does not recognize any protein in whole-cell lysates of B. bronchiseptica or B. parapertussis. Supernatants of cultures of B. pertussis 18323 contain the 60 kDa form of the protein. Southern blot analysis of chromosomal DNA from strains of B. bronchiseptica and B. parapertussis, using a probe derived from tcfA, shows strong hybridization only to B. pertussis DNA. Thus, Tcf appears to be a unique virulence factor of B. pertussis.

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Section: Discussionsupporting

confidence: 91%

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Finn

Stevens

1995

Molecular Microbiology

110

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“…Interestingly, a later study showed that the complete Fim mutant induced a more severe lung inflammation compared with an FHA mutant and the wild-type strain, suggesting that Fim may also act as an immunosuppressant (Vandebriel et al, 2003). Kimura et al (1990) found that FHA was important only for initial colonization of the mouse trachea, but not for colonization of the lungs. In summary, these animal studies suggest an especially important role for fimbriae in colonization, but also imply FHA and Prn in this process.…”

Section: Importance Of Adhesins and Toxins For Colonization In Animalmentioning

confidence: 96%

Pertussis: a matter of immune modulation

et al. 2011

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Pertussis, or whooping cough, is a highly contagious, acute respiratory disease of humans that is caused by the Gram-negative bacterial pathogen Bordetella pertussis. In the face of extensive global vaccination, this extremely monomorphic pathogen has persisted and re-emerged, causing approximately 300,000 deaths each year. In this review, we discuss the interaction of B. pertussis with the host mucosal epithelium and immune system. Using a large number of virulence factors, B. pertussis is able to create a niche for colonization in the human respiratory tract. The successful persistence of this pathogen is mainly due to its ability to interfere with almost every aspect of the immune system, from the inhibition of complement- and phagocyte-mediated killing to the suppression of T- and B-cell responses. Based on these insights, we delineate ideas for the rational design of improved vaccines that can target the 'weak spots' in the pathogenesis of this highly successful pathogen.

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“…Studies aimed at determining roles for FHA in vivo using B. pertussis and mouse models have yielded conflicting data, with most failing to reveal any difference between wild-type and FHA-deficient bacteria (Weiss and Goodwin, 1989;Goodwin and Weiss, 1990;Kimura et al, 1990;Roberts et al, 1993;Khelef et al, 1994;Alonso et al, 2001;McGuirk et al, 2002). Lack of a clear phenotype for fhaB mutants in these studies may be due to the fact that mice are not natural-hosts for B. pertussis.…”

Section: Introductionmentioning

confidence: 99%

Natural‐host animal models indicate functional interchangeability between the filamentous haemagglutinins of Bordetella pertussis and Bordetella bronchiseptica and reveal a role for the mature C‐terminal domain, but not the RGD motif, during infection

Julio

Inatsuka

Mazar

et al. 2009

Molecular Microbiology

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Summary Bacteria of the Bordetella genus cause respiratory tract infections. Both broad host range (e.g. Bordetella bronchiseptica) and human-adapted (e.g. Bordetella pertussis) strains produce a surface-exposed and secreted protein called filamentous haemagglutinin (FHA) that functions in adherence and immunomodulation. Previous studies using B. pertussis and cultured mammalian cells identified several FHA domains with potential roles in host cell interactions, including an Arg-Gly-Asp (RGD) triplet that was reported to bind integrins on epithelial cells and monocytes to activate host signalling pathways. We show here that, in contrast to our previous report, the fhaB genes of B. pertussis and B. bronchiseptica are functionally interchangeable, at least with regard to the various in vitro and in vivo assays investigated. This result is significant because it indicates that information obtained studying FHA using B. bronchiseptica and natural-host animal models should apply to B. pertussis FHA as well. We also show that the C-terminus of mature FHA, which we name the MCD, mediates adherence to epithelial and macrophage-like cells and is required for colonization of the rat respiratory tract and modulation of the inflammatory response in mouse lungs. We could not, however, detect a role for the RGD in any of these processes.

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Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model

Cited by 147 publications

References 37 publications

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

Pertussis: a matter of immune modulation

Natural‐host animal models indicate functional interchangeability between the filamentous haemagglutinins of Bordetella pertussis and Bordetella bronchiseptica and reveal a role for the mature C‐terminal domain, but not the RGD motif, during infection

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