Bordetella parapertussis adenylate cyclase toxin promotes the bacterial survival to the encounter with macrophages. (January 2023)

• Record Type: Journal Article
• Authors: Carrica, Mariela del Carmen; Gorgojo, Juan Pablo; Lamberti, Yanina Andrea; Valdez, Hugo Alberto; Rodriguez, Maria Eugenia
• Is Part Of: Microbial pathogenesis. Volume 174(2023)
• Publication Date: 2023-01
• Subjects: Bordetella parapertussis -- Adenylate cyclase -- Macrophage -- Cytotoxicity -- Intracellular survival; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105898
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: 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. Highlights: 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.