Mechanism of association of adenylate cyclase toxin with the surface of <i>Bordetella pertussis</i>: a role for toxin–filamentous haemagglutinin interaction

Zaretzky, Franca R.; Gray, Mary C.; Hewlett, Erik L.

doi:10.1046/j.1365-2958.2002.03107.x

Cited by 61 publications

(87 citation statements)

References 52 publications

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“…AC-Hly toxin thus conserved both its pore-forming haemolytic activity and its AC activity whether it was produced in a PRN-deficient or in a PRN-producing isolate. The absence of PRN production does not impact the distribution of AC activity as over 90 % remained surface bound whatever the phenotype of the isolate (Table 1), which is consistent with published observations (Zaretzky et al, 2002).…”

Section: Ac Activity and Secretionsupporting

confidence: 91%

“…In vitro studies, however, demonstrated that AC-Hly interacts with FHA (Zaretzky et al, 2002) and it has been hypothesized that PRN might interact with this toxin as well (Khelef & Guiso, 1995). These interactions may participate in pertussis pathogenesis since a higher concentration of AC-Hly is localized at the site of adhesion through non-covalent interaction with FHA (Zaretzky et al, 2002), while AC-Hly seems mandatory for optimal FHA binding activity to epithelial cells (Perez Vidakovics et al, 2006). We here demonstrate that loss of PRN production does not impact AC-Hly-related phenotypes, whereas the presence of specific anti-FHA or anti-PRN antibodies does.…”

Section: Discussionmentioning

confidence: 99%

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Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Hégerlé

Guiso

2014

Microbiology

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Whooping cough is a vaccine-preventable disease presenting with epidemic cycles linked to natural and/or vaccine-driven evolution of the aetiological agent of the disease, Bordetella pertussis. Adenylate cyclase-haemolysin (AC-Hly) is a major toxin produced by this pathogen, which mediates macrophage apoptosis in vitro and in vivo. While current acellular pertussis vaccine (APV) formulations do not include AC-Hly, they all contain pertussis toxin and can comprise filamentous haemagglutinin (FHA), which interacts with AC-Hly, and pertactin (PRN), which has been hypothesized also to interact with AC-Hly. We aimed to study the capacity of specific antibodies to inhibit the in vitro B. pertussis AC-Hly-mediated cytotoxicity of J774A.1 murine macrophages in a background of a changing bacterial population. We demonstrate that: (i) clinical isolates of different types or PRN phenotype are all cytotoxic and lethal in the mouse model of respiratory infection; (ii) lack of PRN production does not impact AC-Hly-related phenotypes; (iii) anti-AC-Hly antibodies inhibit cell lysis whatever the phenotype of the isolate, while anti-PRN antibodies significantly inhibit cell lysis provided the isolate produces this antigen, which might be relevant in vivo for APV-induced immunity; and (iv) anti-FHA antibodies only inhibit lysis induced by isolates collected in 2012, maybe indicating specific characteristics of epidemic lineages of B. pertussis.

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Section: Ac Activity and Secretionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Hégerlé

Guiso

2014

Microbiology

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“…This suggests that ACY suppresses biofilm formation in B. bronchiseptica. A previous report has demonstrated a direct protein-protein interaction of ACY with FHA (36). Because FHA appears to be a major contributor to biofilm formation in B. bronchiseptica, we propose that ACY may inhibit biofilm formation via its interaction with FHA.…”

Section: B Bronchiseptica Generates a Maximal Biofilm Phenotype In Tmentioning

confidence: 57%

“…It also plays an important role in the interaction of the bacteria with neutrophils in vivo (11). However, ACY has also been shown to be associated with the cell surface of Bordetella and can bind specifically to FHA in vitro (36). ACY is highly expressed in the Bvg ϩ phase but is significantly downregulated in the Bvg i phase (8).…”

mentioning

confidence: 99%

The Bvg Virulence Control System Regulates Biofilm Formation in Bordetella bronchiseptica

2004

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؉ phase encode known virulence factors, including adhesins such as filamentous hemagglutinin (FHA) and fimbriae, as well as toxins such as the bifunctional adenylate cyclase/hemolysin (ACY). Previous studies showed that in the Bvg i phase, FHA and fimbriae continue to be expressed, but ACY expression is significantly downregulated. In this report, we determine that Bordetella bronchiseptica can form biofilms in vitro and that the generation of biofilm is maximal in the Bvg i phase. We show that FHA is required for maximal biofilm formation and that fimbriae may also contribute to this phenotype. However, expression of ACY inhibits biofilm formation, most likely via interactions with FHA. Therefore, the coordinated regulation of adhesins and ACY expression leads to maximal biofilm formation in the Bvg i phase in B. bronchiseptica.Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related gram-negative coccobacilli that colonize the upper respiratory tract of mammals. B. pertussis and most B. parapertussis strains are obligate human pathogens that usually cause acute respiratory diseases. B. bronchiseptica has a much broader host range and is considered to be representative of the evolutionary progenitor of all Bordetella spp. (10, 27). It naturally infects many laboratory animals, including mice, rats, and rabbits, and thus serves as an ideal model for studying bacterial pathogenesis in a natural infection setting. Although B. bronchiseptica has been associated with various respiratory diseases, infection by this organism generally leads to chronic and asymptomatic colonization in the host. This lifestyle indicates that the bacteria employ specific mechanisms to counteract host immune responses and also implies successful interactions with other commensal bacteria commonly found in the upper respiratory tract.

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“…Given that the structure of B. hinzii ACT is presumably the same as B. pertussis ACT based on sequence data, this may reflect a difference in toxin extractability/accessibility between the strains. RTX toxins in general, and ACT in particular, are known to interact with LPS and other surface molecules, affecting both protein conformation and biological activity (5,17,67,95). B. hinzii produces an LPS with an O-specific polysaccharide chain which differs significantly from other smooth-type LPS-containing Bordetella strains (such as B. bronchiseptica), as well as B. pertussis, which lacks an O-chain altogether (3,11,85).…”

Section: Discussionmentioning

confidence: 99%

Adenylate Cyclase Toxin (ACT) fromBordetella hinzii: Characterization and Differences from ACT ofBordetella pertussis

et al. 2005

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Bordetella hinzii is a commensal respiratory microorganism in poultry but is increasingly being recognized as an opportunistic pathogen in immunocompromised humans. Although associated with a variety of disease states, practically nothing is known about the mechanisms employed by this bacterium. In this study, we show by DNA sequencing and reverse transcription-PCR that both commensal and clinical strains of B. hinzii possess and transcriptionally express cyaA, the gene encoding adenylate cyclase toxin (ACT) in other pathogenic Bordetella species. By Western blotting, we also found that B. hinzii produces full-length ACT protein in quantities that are comparable to those made by B. pertussis. In contrast to B. pertussis ACT, however, ACT from B. hinzii is less extractable from whole bacteria, nonhemolytic, has a 50-fold reduction in adenylate cyclase activity, and is unable to elevate cyclic AMP levels in host macrophages (nontoxic). The decrease in enzymatic activity is attributable, at least in part, to a decreased binding affinity of B. hinzii ACT for calmodulin, the eukaryotic activator of B. pertussis ACT. In addition, we demonstrate that the lack of intoxication by B. hinzii ACT may be due to the absence of expression of cyaC, the gene encoding the accessory protein required for the acylation of B. pertussis ACT. These results demonstrate the expression of ACT by B. hinzii and represent the first characterization of a potential virulence factor of this organism.

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Mechanism of association of adenylate cyclase toxin with the surface of Bordetella pertussis: a role for toxin–filamentous haemagglutinin interaction

Cited by 61 publications

References 52 publications

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

The Bvg Virulence Control System Regulates Biofilm Formation in Bordetella bronchiseptica

Adenylate Cyclase Toxin (ACT) fromBordetella hinzii: Characterization and Differences from ACT ofBordetella pertussis

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