Identification of Bordetella pertussis virulence-associated outer membrane proteins

Rossi, Juan Pablo F.C.

doi:10.1016/s0378-1097(99)00009-9

Cited by 10 publications

(12 citation statements)

References 23 publications

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“…N-terminal sequencing of proteins from outer membrane preparations of B. pertussis has localized the processing of BrkA to between Asn 731 and Ala 732 (25), resulting in a ␤-domain of 30 kDa (28). At 30 kDa, the BrkA ␤-domain is smaller than the ␤-domains for IgA protease, VirG/IcsA, and AIDA-1, but it approaches the size of the outer membraneembedded ␤-cores identified for these proteins (11,19,31).…”

Section: Resultsmentioning

confidence: 99%

“…Following translocation, the cleaved ␣-domain remains tightly associated with the bacterial surface and is not detected in B. pertussis culture supernatants (24). The processed ␤-domain has been isolated from B. pertussis outer membrane fractions, and the processing site has been determined to occur between residues Asn 731 and Ala 732 (25). In an effort to elucidate the mechanism(s) of autotransporter secretion, we have begun to characterize BrkA secretion.…”

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confidence: 99%

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Identification of Secretion Determinants of theBordetella pertussisBrkA Autotransporter

2003

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The autotransporters comprise a functionally diverse family of gram-negative proteins that mediate their own export across the bacterial outer membrane. They consist of an amino-terminal passenger region called the "␣-domain" and the structural hallmark of the autotransporter family, a carboxy-terminal transporter region usually referred to as the "␤-domain." The passenger region can be quite diverse and constitutes the effector functions of these proteins, whereas the C-terminal region is conserved and is responsible for translocating the passenger moiety across the outer membrane. BrkA is the 103-kDa autotransporter protein in Bordetella pertussis that is cleaved to yield a 73-kDa N-terminal ␣-domain and a 30-kDa C-terminal ␤-domain. We have previously shown that a recombinant form of the ␤-domain of BrkA is capable of forming channels in artificial membranes. Here, we define two additional secretion determinants of BrkA. N-terminal sequencing of the 73-kDa BrkA passenger from B. pertussis and Escherichia coli revealed that BrkA has a 42-amino-acid signal peptide. In addition, deletion analysis of BrkA identified a 31-to 39-amino-acid region found immediately upstream of the ␤-domain that was essential for surface expression. This 31-to 39-amino-acid linker region, together with the ␤-domain, defines the minimal BrkA translocation unit. The linker region may also serve to anchor the BrkA passenger to the bacterial surface.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Identification of Secretion Determinants of theBordetella pertussisBrkA Autotransporter

2003

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“…The brk locus contains two divergently transcribed open reading frames (ORFs), brkA and brkB, with a putative bvgA-binding site between them. BrkA is a 103-kDa autotransporter protein, containing a 73-kDa ␣-domain, or passenger domain, and a 30-kDa ␤-domain, which acts as the transporter (20,21,25). It is similar in sequence to pertactin, possessing two RGD motifs, an outer membrane localization signal, and a proteolytic cleavage site.…”

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confidence: 99%

Strain-Dependent Role of BrkA duringBordetella pertussisInfection of the Murine Respiratory Tract

Elder

Harvill

2004

Infect Immun

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Bordetella pertussis, the causative agent of whooping cough, expresses many virulence factors believed to be involved in infection and disease progression. While these factors as a group are required for infection, deletion of individual virulence factor genes generally has limited effects on the ability of B. pertussis to efficiently infect the respiratory tract of mice, suggesting they may perform noncritical or redundant functions. We have recently observed that a B. pertussis strain, putatively with a mutation of a single gene, brkA, results in a severe defect in vivo. Although BrkA has been shown to be required for B. pertussis to resist complement-mediated killing in vitro, the relevance of these findings to the in vivo role of BrkA during infection has not been examined. Transducing this mutation into multiple wild-type B. pertussis strains allowed us to confirm the in vitro phenotype of reduced resistance to serum complement. All ⌬brkA mutants were increased in their sensitivity to complement in vitro, both in the presence and absence of antibodies. However, these strains differed substantially in their phenotypes in vivo. ⌬brkA mutants of recent clinical isolates were indistinguishable from wild-type strains in their efficient infection of respiratory organs, suggesting that the function of BrkA in these strains is noncritical or redundant. In contrast, multiple ⌬brkA strains derived from Tohama I were severely defective during the first week postinoculation compared to their wild-type parent. This defect was present even in complement-deficient mice, revealing a complement-independent phenotype for the ⌬brkA mutant in respiratory tract infection.Bordetella pertussis, the causative agent of whooping cough, contains the bvgAS two-component system that controls the expression of many virulence factors, including pertussis toxin, adenylate cyclase, dermonecrotic toxin, filamentous hemagglutinin, fimbriae, pertactin, and BrkA (Bordetella resistance to serum killing) (3,7,28). As a group, these bvg-regulated proteins have been shown to be important factors in effective infection and disease progression. B. pertussis mutants locked in the Bvg Ϫ phase, in which the expression of multiple virulence factors is decreased, are rapidly cleared from the respiratory tracts of inoculated mice (5, 16), but deletions of single virulence factors have varying, less-severe effects on colonization, suggesting that they may perform noncritical or redundant functions (18).

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“…Using feeding assays, the iron source substrates for the putative receptors encoded by these genes could not be identified: mutants retained the ability to use heme, enterobactin, desferrioxamine B and ferrichrome. Passerini de Rossi and colleagues identified a 90-kDal outer membrane protein in wild-type B. pertussis that was absent in an isogenic bvgS mutant (Passerini de Rossi et al 1999). Interestingly, this protein was later identified as the TonB-dependent receptor BfrD and expression of bfrD was determined to be activated by the BvgAS signal transduction system involved in virulence gene regulation (Antoine et al 2000).…”

Section: Xenosiderophores and Tonb-dependent Receptorsmentioning

confidence: 99%

Bordetella iron transport and virulence

2007

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Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are pathogens with a complex iron starvation stress response important for adaptation to nutrient limitation and flux in the mammalian host environment. The iron starvation stress response is globally regulated by the Fur repressor using ferrous iron as the co-repressor. Expression of iron transport system genes of Bordetella is coordinated by priority regulation mechanisms that involve iron source sensing. Iron source sensing is mediated by distinct transcriptional activators that are responsive to the cognate iron source acting as the inducer.

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Identification of Bordetella pertussis virulence-associated outer membrane proteins

Cited by 10 publications

References 23 publications

Identification of Secretion Determinants of theBordetella pertussisBrkA Autotransporter

Identification of Secretion Determinants of theBordetella pertussisBrkA Autotransporter

Strain-Dependent Role of BrkA duringBordetella pertussisInfection of the Murine Respiratory Tract

Bordetella iron transport and virulence

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