scholarly journals Pertussis toxin and adenylate cyclase toxin: key virulence factors ofBordetella pertussisand cell biology tools

2010 ◽  
Vol 5 (3) ◽  
pp. 455-469 ◽  
Author(s):  
Nicholas H Carbonetti
Keyword(s):  
Adenylate Cyclase ◽  
Virulence Factors ◽  
Pertussis Toxin ◽  
Cell Biology ◽  
Adenylate Cyclase Toxin

scholarly journals Bordetella pertussis Virulence Factors Affect Phagocytosis by Human Neutrophils

2000 ◽  
Vol 68 (3) ◽  
pp. 1735-1739 ◽  
Author(s):  
Christine L. Weingart ◽  
Alison A. Weiss
Keyword(s):  
Adenylate Cyclase ◽  
Virulence Factors ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Type Strain ◽  
Wild Type Strain ◽  
Human Neutrophils ◽  
Wild Type ◽  
Dermonecrotic Toxin ◽  
Adenylate Cyclase Toxin

ABSTRACT The interaction between human neutrophils and wild-typeBordetella pertussis or mutants expressing altered lipopolysaccharide or lacking virulence factors—pertussis toxin, adenylate cyclase toxin, dermonecrotic toxin, filamentous hemagglutinin (FHA), pertactin, or BrkA—was examined. In the absence of antibodies, the wild-type strain and the mutants, with the exception of mutants lacking FHA, attached efficiently to neutrophils. The addition of opsonizing antibodies caused a significant reduction (approximately 50%) in attachment of the wild-type strain and most of the mutants expressing FHA, suggesting that bacterium-mediated attachment is more efficient than Fc-mediated attachment. Phagocytosis was also examined. In the absence of antibodies, about 12% of the wild-type bacteria were phagocytosed. Opsonization caused a statistically significant reduction in phagocytosis (to 3%), possibly a consequence of reduced attachment. Phagocytosis of most of the mutants was similar to that of the wild type, with the exception of the mutants lacking adenylate cyclase toxin. About 70% of the adenylate cyclase toxin mutants were phagocytosed, but only in the presence of opsonizing antibody, suggesting that Fc receptor-mediated signaling may be needed for phagocytosis. These studies indicate that FHA mediates attachment ofB. pertussis to neutrophils, but adenylate cyclase toxin blocks phagocytosis.

scholarly journals Pertussis Toxin and Adenylate Cyclase Toxin Provide a One-Two Punch for Establishment of Bordetella pertussis Infection of the Respiratory Tract

2005 ◽  
Vol 73 (5) ◽  
pp. 2698-2703 ◽  
Author(s):  
Nicholas H. Carbonetti ◽  
Galina V. Artamonova ◽  
Charlotte Andreasen ◽  
Nicholas Bushar
Keyword(s):  
Adenylate Cyclase ◽  
Respiratory Tract ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Type Strain ◽  
Wild Type Strain ◽  
Infection Model ◽  
Wild Type ◽  
Adenylate Cyclase Toxin ◽  
Tract Infections

ABSTRACT Previously we found that pertussis toxin (PT), an exotoxin virulence factor produced by Bordetella pertussis, plays an important early role in colonization of the respiratory tract by this pathogen, using a mouse intranasal infection model. In this study, we examined the early role played by another exotoxin produced by this pathogen, adenylate cyclase toxin (ACT). By comparing a wild-type strain to a mutant strain (ΔCYA) with an in-frame deletion of the cyaA gene encoding ACT, we found that the lack of ACT confers a significant peak (day 7) colonization defect (1 to 2 log10). In mixed-infection experiments, the ΔCYA strain was significantly outcompeted by the wild-type strain, and intranasal administration of purified ACT did not increase colonization by ΔCYA. These data suggest that ACT benefits the bacterial cells that produce it and, unlike PT, does not act as a soluble factor benefiting the entire infecting bacterial population. Comparison of lower respiratory tract infections over the first 4 days after inoculation revealed that the colonization defect of the PT deletion strain was apparent earlier than that of ΔCYA, suggesting that PT plays an earlier role than ACT in the establishment of B. pertussis infection. Examination of cells in the bronchoalveolar lavage fluid of infected mice revealed that, unlike PT, ACT does not appear to inhibit neutrophil influx to the respiratory tract early after infection but may combat neutrophil activity once influx has occurred.

scholarly journals The Eukaryotic Host Factor 14-3-3 Inactivates Adenylate Cyclase Toxins ofBordetella bronchisepticaandB. parapertussis, but NotB. pertussis

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Aya Fukui-Miyazaki ◽  
Hirono Toshima ◽  
Yukihiro Hiramatsu ◽  
Keisuke Okada ◽  
Keiji Nakamura ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Adenylate Cyclase ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Bordetella Pertussis ◽  
Host Factor ◽  
Target Cells ◽  
Content Type ◽  
Functional Differences ◽  
Adenylate Cyclase Toxin

ABSTRACTBordetella pertussis,Bordetella bronchiseptica, andBordetella parapertussisshare highly homologous virulence factors and commonly cause respiratory infections in mammals; however, their host specificities and disease severities differ, and the reasons for this remain largely unknown. Adenylate cyclase toxin (CyaA) is a homologous virulence factor that is thought to play crucial roles inBordetellainfections. We herein demonstrate that CyaAs function as virulence factors differently betweenB. bronchiseptica/B. parapertussisandB. pertussis.B.bronchisepticaCyaA bound to target cells, and its enzyme domain was translocated into the cytosol similarly toB.pertussisCyaA. The hemolytic activity ofB.bronchisepticaCyaA on sheep erythrocytes was also preserved. However, in nucleated target cells,B.bronchisepticaCyaA was phosphorylated at Ser375, which constitutes a motif (RSXpSXP [pS is phosphoserine]) recognized by the host factor 14-3-3, resulting in the abrogation of adenylate cyclase activity. Consequently, the cytotoxic effects ofB.bronchisepticaCyaA based on its enzyme activity were markedly attenuated.B.parapertussisCyaA carries the 14-3-3 motif, indicating that its intracellular enzyme activity is abrogated similarly toB.bronchisepticaCyaA; however,B.pertussisCyaA has Phe375instead of Ser, and thus, was not affected by 14-3-3. In addition,B.pertussisCyaA impaired the barrier function of epithelial cells, whereasB.bronchisepticaCyaA did not. Rat infection experiments suggested that functional differences in CyaA are related to differences in pathogenicity betweenB. bronchiseptica/B.parapertussisandB. pertussis.IMPORTANCEBordetella pertussis,B. bronchiseptica, andB. parapertussisare bacterial respiratory pathogens that are genetically close to each other and produce many homologous virulence factors; however, their host specificities and disease severities differ, and the reasons for this remain unknown. Previous studies attempted to explain these differences by the distinct virulence factors produced by eachBordetellaspecies. In contrast, we indicated functional differences in adenylate cyclase toxin, a homologous virulence factor ofBordetella. The toxins ofB. bronchisepticaand presumablyB. parapertussiswere inactivated by the host factor 14-3-3 after phosphorylation in target cells, whereas theB. pertussistoxin was not inactivated because of the lack of the phosphorylation site. This is the first study to show that 14-3-3 inactivates the virulence factors of pathogens. The present results suggest that pathogenic differences inBordetellaare attributed to the different activities of adenylate cyclase toxins.

scholarly journals Simultaneous Determination of Antibodies to Pertussis Toxin and Adenylate Cyclase Toxin Improves Serological Diagnosis of Pertussis

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 180
Author(s):  
Aapo Knuutila ◽  
Alex-Mikael Barkoff ◽  
Jussi Mertsola ◽  
Radim Osicka ◽  
Peter Sebo ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Pertussis Toxin ◽  
Serological Diagnosis ◽  
Promising Candidate ◽  
Flow Test ◽  
Before And After ◽  
Adenylate Cyclase Toxin ◽  
Lateral Flow Test ◽  
Acellular Vaccines

Serological diagnosis of pertussis is mainly based on anti-pertussis toxin (PT) IgG antibodies. Since PT is included in all acellular vaccines (ACV), serological assays do not differentiate antibodies induced by ACVs and infection. Adenylate cyclase toxin (ACT) is not included in the ACVs, which makes it a promising candidate for pertussis serology with the specific aim of separating infection- and ACV-induced antibodies. A multiplex lateral flow test with PT and ACT antigens was developed to measure serum antibodies from pertussis-seropositive patients (n = 46), healthy controls (n = 102), and subjects who received a booster dose of ACV containing PT, filamentous hemagglutinin, and pertactin (n = 67) with paired sera collected before and one month after the vaccination. If the diagnosis was solely based on anti-PT antibodies, 98.5–44.8% specificity (before and after vaccination, respectively) and 78.2% sensitivity were achieved, whereas if ACT was used in combination with PT, the sensitivity of the assay increased to 91.3% without compromising specificity. No increase in the level of anti-ACT antibodies was found after vaccination. This exploratory study indicates that the use of ACT for serology would be beneficial in combination with a lower quantitative cutoff for anti-PT antibodies, and particularly in children and adolescents who frequently receive booster vaccinations.

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