scholarly journals Bordetella pertussis filamentous hemagglutinin interacts with a leukocyte signal transduction complex and stimulates bacterial adherence to monocyte CR3 (CD11b/CD18).

1994 ◽  
Vol 180 (4) ◽  
pp. 1225-1233 ◽  
Author(s):  
Y Ishibashi ◽  
S Claus ◽  
D A Relman
Keyword(s):  
Signal Transduction ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Bacterial Pathogen ◽  
Binding Activity ◽  
Host Cells ◽  
Bacterial Surface ◽  
Filamentous Hemagglutinin ◽  
Complement Receptor 3 ◽  
Leukocyte Response

Bordetella pertussis, the causative agent of whooping cough, adheres to human monocytes/macrophages by means of a bacterial surface-associated protein, filamentous hemagglutinin (FHA) and the leukocyte integrin, complement receptor 3 (CR3, alpha M beta 2, CD11b/CD18). We show that an FHA Arg-Gly-Asp site induces enhanced B. pertussis binding to monocytes, and that this enhancement is blocked by antibodies directed against CR3. Enhancement requires a monocyte signal transduction complex, composed of leukocyte response integrin (alpha? beta 3) and integrin-associated protein (CD47). This complex is known to upregulate CR3 binding activity. Thus, a bacterial pathogen enhances its own attachment to host cells by coopting a host cell signaling pathway.

scholarly journals Production of Nontypeable Haemophilus influenzae HtrA by Recombinant Bordetella pertussis with the Use of Filamentous Hemagglutinin as a Carrier

2005 ◽  
Vol 73 (7) ◽  
pp. 4295-4301 ◽  
Author(s):  
Sylvie Alonso ◽  
Eve Willery ◽  
Genevieve Renauld-Mongénie ◽  
Camille Locht
Keyword(s):  
Immune Responses ◽  
Haemophilus Influenzae ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Etiologic Agent ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Surface ◽  
Filamentous Hemagglutinin ◽  
Bacterial Vector ◽  
Antibody Titers

ABSTRACT Bordetella pertussis, the etiologic agent of whooping cough, is a highly infectious human pathogen capable of inducing mucosal and systemic immune responses upon a single intranasal administration. In an attenuated, pertussis toxin (PTX)-deficient recombinant form, it may therefore constitute an efficient bacterial vector that is particularly well adapted for the delivery of heterologous antigens to the respiratory mucosa. Filamentous hemagglutinin (FHA) has been used as a carrier to present foreign antigens at the bacterial surface, thereby inducing local, systemic, and protective immune responses to these antigens in mice. Both full-length and truncated (Fha44) forms of FHA have been used for antigen presentation. To investigate the effect of the carrier (FHA or Fha44) on antibody responses to passenger antigens, we genetically fused the HtrA protein of nontypeable Haemophilus influenzae to either FHA form. The fha-htrA and Fha44 gene-htrA hybrids were expressed as single copies inserted into the chromosome of PTX-deficient B. pertussis. Both chimeras were secreted into the culture supernatants of the recombinant strains and were recognized by anti-FHA and anti-HtrA antibodies. Intranasal infection with the strain producing the FHA-HtrA hybrid led to significantly higher anti-HtrA and anti-FHA antibody titers than those obtained in mice infected with the Fha44-HtrA-producing strain. Interestingly, the B. pertussis strain producing the Fha44-HtrA chimera colonized the mouse lungs more efficiently than the parental, Fha44-producing strain and gave rise to higher anti-FHA antibody titers than those induced by the parental strain.

scholarly journals DegP initiates regulated processing of filamentous hemagglutinin in Bordetella bronchiseptica

2021 ◽  
Author(s):  
Richard M Johnson ◽  
Zachary M Nash ◽  
Margaret R Dedloff ◽  
John C Shook ◽  
Peggy A Cotter
Keyword(s):  
Pathogenic Bacteria ◽  
Whooping Cough ◽  
Bordetella Bronchiseptica ◽  
Host Cells ◽  
Closely Related Species ◽  
Bacterial Surface ◽  
Filamentous Hemagglutinin ◽  
C Terminus ◽  
Cell Clearance ◽  
Culture Supernatants

Filamentous hemagglutinin (FhaB) is a critical virulence factor for both Bordetella bronchiseptica, the causal agent of whooping cough, and the closely related species Bordetella bronchiseptica. FhaB is an adhesin, suppresses inflammatory cytokine production, and protects against phagocytic cell clearance during infection. Regulated degradation of the FhaB C-terminal prodomain is required to establish a persistent infection in mice. Two proteases, CtpA in the periplasm and SphB1 on the bacterial surface, mediate FhaB processing, and we recently determined that CtpA functions before, and controls the FhaB cleavage site of, SphB1. However, the data indicate that another periplasmic protease must initiate degradation of the prodomain by removing a portion of the FhaB C terminus that inhibits CtpA-mediated degradation. Using a candidate approach, we identified DegP as the initiating protease. Deletion of degP or substitution of its predicted catalytic residue resulted in reduced creation of FHA', the main product of FhaB processing, and an accumulation of full-length FhaB in whole cell lysates. Also, FHA' was no longer released into culture supernatants in degP mutants. Alterations of the FhaB C terminus that relieve inhibition of CtpA abrogate the need for DegP, consistent with DegP functioning prior to CtpA in the processing pathway. DegP is not required for secretion of FhaB through FhaC or for adherence of the bacteria to host cells, indicating that DegP acts primarily as a protease and not a chaperone for FhaB in B. bronchiseptica. Our results highlight a role for HtrA family proteases in activation of virulence factors in pathogenic bacteria.

scholarly journals Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis

2019 ◽  
Vol 20 (12) ◽  
pp. 3073 ◽  
Author(s):  
Ana Dienstbier ◽  
Fabian Amman ◽  
Daniel Štipl ◽  
Denisa Petráčková ◽  
Branislav Večerek
Keyword(s):  
Gene Expression ◽  
Bordetella Pertussis ◽  
Transcriptional Control ◽  
Whooping Cough ◽  
Expression Profiles ◽  
Bacterial Pathogen ◽  
Gene Expression Profiles ◽  
Control Of Gene Expression ◽  
Proteomic Data

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r2 = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene.

scholarly journals Role of Adhesin Release for Mucosal Colonization by a Bacterial Pathogen

2003 ◽  
Vol 197 (6) ◽  
pp. 735-742 ◽  
Author(s):  
Loïc Coutte ◽  
Sylvie Alonso ◽  
Nathalie Reveneau ◽  
Eve Willery ◽  
Brigitte Quatannens ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Wild Type ◽  
Early Step ◽  
Bacterial Surface ◽  
Extracellular Milieu ◽  
Wild Type Parent

Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied. To address the role of adhesin release in pathogenesis, we used Bordetella pertussis as a model, since its major adhesin, filamentous hemagglutinin (FHA), partitions between the bacterial surface and the extracellular milieu. FHA release depends on its maturation by the specific B. pertussis protease SphB1. We constructed SphB1-deficient mutants and found that they were strongly affected in their ability to colonize the mouse respiratory tract, although they adhered even better to host cells in vitro than their wild-type parent strain. The defect in colonization could be overcome by prior nasal instillation of purified FHA or by coinfection with FHA-releasing B. pertussis strains, but not with SphB1-producing FHA-deficient strains, ruling out a nonspecific effect of SphB1. These results indicate that the release of FHA is important for colonization, as it may facilitate the dispersal of bacteria from microcolonies and the binding to new sites in the respiratory tract.

scholarly journals The Glycan-Rich Outer Layer of the Cell Wall of Mycobacterium tuberculosis Acts as an Antiphagocytic Capsule Limiting the Association of the Bacterium with Macrophages

2004 ◽  
Vol 72 (10) ◽  
pp. 5676-5686 ◽  
Author(s):  
Richard W. Stokes ◽  
Raymond Norris-Jones ◽  
Donald E. Brooks ◽  
Terry J. Beveridge ◽  
Dan Doxsee ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Surface Hydrophobicity ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Mammalian Host ◽  
Human Macrophage ◽  
Bacterial Surface ◽  
Important Virulence Factor ◽  
Complement Receptor 3 ◽  
Macrophage Populations

ABSTRACT Mycobacterium tuberculosis, the causative agent of tuberculosis, is a facultative intracellular pathogen that infects macrophages and other host cells. We show that sonication of M. tuberculosis results in the removal of material from the surface capsule-like layer of the bacteria, resulting in an enhanced propensity of the bacteria to bind to macrophages. This effect is observed with disparate murine and human macrophage populations though, interestingly, not with freshly explanted alveolar macrophages. Enhanced binding to macrophages following sonication is significantly greater within members of the M. tuberculosis family (pathogens) than within the Mycobacterium avium complex (opportunistic pathogens) or for Mycobacterium smegmatis (saprophyte). Sonication does not affect the viability or the surface hydrophobicity of M. tuberculosis but does result in changes in surface charge and in the binding of mannose-specific lectins to the bacterial surface. The increased binding of sonicated M. tuberculosis was not mediated through complement receptor 3. These results provide evidence that the surface capsule on members of the M. tuberculosis family may be an important virulence factor involved in the survival of M. tuberculosis in the mammalian host. They also question the view that M. tuberculosis is readily ingested by any macrophage it encounters and support the contention that M. tuberculosis, like many other microbial pathogens, has an antiphagocytic capsule that limits and controls the interaction of the bacterium with macrophages.

Antibodies To Filamentous Hemagglutinin Of Bordetella Pertussis And Protection Against Whooping Cough In Schoolchildren

1994 ◽  
Vol 170 (3) ◽  
pp. 705-708 ◽  
Author(s):  
Q. He ◽  
M. K. Viljanen ◽  
R.-M. Olander ◽  
H. Bogaerts ◽  
D. De Grave ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Filamentous Hemagglutinin

scholarly journals Peptide-Based Inhibitors of Fimbrial Biogenesis inPorphyromonas gingivalis

2019 ◽  
Vol 87 (3) ◽  
Author(s):  
Sarah R. Alaei ◽  
Jin Ho Park ◽  
Stephen G. Walker ◽  
David G. Thanassi
Keyword(s):  
Periodontal Disease ◽  
Bacterial Pathogen ◽  
Proteolytic Processing ◽  
Host Cells ◽  
Content Type ◽  
Bacterial Surface ◽  
Fimbrial Subunit ◽  
Biofilm Model ◽  
Assembly Mechanism ◽  
And Function

ABSTRACTPeriodontitis is a progressive inflammatory disease that affects roughly half of American adults. Colonization of the oral cavity by the Gram-negative bacterial pathogenPorphyromonas gingivalisis a key event in the initiation and development of periodontal disease. Adhesive surface structures termed fimbriae (pili) mediate interactions ofP. gingivaliswith other bacteria and with host cells throughout the course of disease. TheP. gingivalisfimbriae are assembled via a novel mechanism that involves proteolytic processing of lipidated precursor subunits and their subsequent polymerization on the bacterial surface. Given their extracellular assembly mechanism and central roles in pathogenesis, theP. gingivalisfimbriae are attractive targets for anti-infective therapeutics to prevent or treat periodontal disease. Here we confirm that conserved sequences in the N and C termini of the Mfa1 fimbrial subunit protein perform critical roles in subunit polymerization. We show that treatment ofP. gingivaliswith peptides corresponding to the conserved C-terminal region inhibits the extracellular assembly of Mfa fimbriae on the bacterial surface. We also show that peptide treatment interferes with the function of Mfa fimbriae by reducingP. gingivalisadhesion toStreptococcus gordoniiin a dual-species biofilm model. Finally, we show that treatment of bacteria with similar peptides inhibits extracellular polymerization of the Fim fimbriae, which are also expressed byP. gingivalis. These results support a donor strand-based assembly mechanism for theP. gingivalisfimbriae and demonstrate the feasibility of using extracellular peptides to disrupt the biogenesis and function of these critical periodontal disease virulence factors.

scholarly journals Eighty-Kilodalton N-Terminal Moiety of Bordetella pertussis Filamentous Hemagglutinin: Adherence, Immunogenicity, and Protective Role

2002 ◽  
Vol 70 (8) ◽  
pp. 4142-4147 ◽  
Author(s):  
Sylvie Alonso ◽  
Nathalie Reveneau ◽  
Kévin Pethe ◽  
Camille Locht
Keyword(s):  
Bordetella Pertussis ◽  
Protective Immunity ◽  
Whooping Cough ◽  
Protective Role ◽  
Wild Type ◽  
Functional Importance ◽  
Extracellular Milieu ◽  
Filamentous Hemagglutinin ◽  
Number Of Factors

ABSTRACT Bordetella pertussis, the etiological agent of whooping cough, produces a number of factors, such as toxins and adhesins, that are required for full expression of virulence. Filamentous hemagglutinin (FHA) is the major adhesin of B. pertussis. It is a protein of approximately 220 kDa, found both associated at the bacterial cell surface and secreted into the extracellular milieu. Despite its importance in B. pertussis pathogenesis and its inclusion in most acellular pertussis vaccines, little is known about the functional importance of individual domains in infection and in the induction of protective immunity. In this study, we analyzed the role of the approximately 80-kDa N-terminal domain of FHA, designated Fha44, in B. pertussis adherence, colonization, and immunogenicity. Although Fha44 contains the complete heparan sulfate-binding domain, it is not sufficient for adherence to epithelial cells or macrophages. It also cannot replace FHA during colonization of the mouse respiratory tract. Infection with a B. pertussis strain producing Fha44 instead of FHA does not induce anti-FHA antibodies, whereas such antibodies can readily be induced by intranasal administration of purified Fha44. In addition, mice immunized with purified Fha44 were protected against challenge with wild-type B. pertussis, indicating that Fha44 contains protective epitopes. Compared to FHA, Fha44 is much smaller and much more soluble and is therefore easier to purify and to store. These advantages may perhaps warrant considering Fha44 for inclusion in acellular pertussis vaccines.

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