Proteomic Signatures of Intracellular Bordetella pertussis in Respiratory Epithelial Cells

Bordetella pertussis is a strictly human-adapted pathogen and the etiologic agent of whooping cough, a reemerging respiratory disease. Current vaccines fail to prevent colonization, and emerging evidence indicates that B. pertussis can establish intracellular infections that may contribute to its persistence. Previous studies showed that this pathogen adapts its phenotype and survives within human macrophages by modulating bactericidal responses through pertussis toxin (PT) and adenylate cyclase toxin (CyaA). Here, we analyzed the proteome of B. pertussis after internalization into epithelial cells, another possible host niche. Proteomic adaptations were mainly associated with metabolic adjustments indicative of a decelerated intracellular metabolism. Using mutant strains, we found that neither PT nor CyaA is required for B. pertussis for survival in epithelial cells, which is consistent with the absence of a detectable stress response in intracellular bacteria. Proteins previously identified as required for B. pertussis intracellular survival within macrophages, such as factors involved in the bacterial adaptation to acidic compartments, proved neither induced by the intracellular environment nor required for intracellular survival within epithelial cells. Collectively, the findings suggest that these epithelial cells may represent a more favorable niche than macrophages for bacterial persistence.