Bordetella parapertussis adenylate cyclase toxin promotes the bacterial survival to the encounter with macrophages

B. parapertussis is a whooping cough etiological agent, whose incidence in the population has increased remarkably. Virulence factors involved in the bacterial infection, however, remain poorly investigated. We here studied the role of adenylate cyclase (CyaA), the main toxin of B. parapertussis, in...

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Bibliographic Details
Published in:Microbial pathogenesis 2023-01, Vol.174, p.105898-105898, Article 105898
Main Authors: Carrica, Mariela del Carmen, Gorgojo, Juan Pablo, Lamberti, Yanina Andrea, Valdez, Hugo Alberto, Rodriguez, Maria Eugenia
Format: Article
Language:English
Subjects:
Adenylate cyclase
Adenylate Cyclase Toxin - genetics
Adenylate Cyclase Toxin - metabolism
antibacterial properties
antimicrobial peptides
bacterial infections
Bordetella parapertussis
Bordetella parapertussis - genetics
Bordetella pertussis - metabolism
cough
Cytotoxicity
etiological agents
Humans
immune evasion
interleukin-10
Intracellular survival
Macrophage
Macrophages
neutrophils
pathogenesis
phagocytosis
protective effect
toxins
transcription (genetics)
virulence
Whooping Cough - prevention & control
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Summary:B. parapertussis is a whooping cough etiological agent, whose incidence in the population has increased remarkably. Virulence factors involved in the bacterial infection, however, remain poorly investigated. We here studied the role of adenylate cyclase (CyaA), the main toxin of B. parapertussis, in the outcome of the bacterial interaction with macrophages. Our results showed that B. parapertussis CyaA intoxicates human macrophages, prevents bacterial phagocytosis and precludes phago-lysosomal fusion eventually promoting the bacterial survival to the encounter with these immune cells. Accordingly, we found that B. parapertussis CyaA induces the transcriptional downregulation of host genes encoding for antimicrobial peptides, proteins involved in bacterial intracellular killing, and the pro-inflammatory cytokine TNF-α, while induces the upregulation of the anti-inflammatory cytokine IL-10. Together with previous reports suggesting a protective role of B. parapertussis CyaA against neutrophils bactericidal activity, the results of this study suggest a central role of CyaA in B. parapertussis immune evasion and persistence. •B. parapertussis CyaA is cytotoxic for macrophages.•B. parapertussis CyaA precludes bacterial uptake by macrophages.•B. parapertussis CyaA promotes the intracellular survival of phagocytosed bacteria.•B. parapertussis CyaA modulates the macrophage bactericidal response.
ISSN:0882-4010
1096-1208
DOI:10.1016/j.micpath.2022.105898