Adenylate cyclase toxin of Bordetella parapertussis disrupts the epithelial barrier granting the bacterial access to the intracellular space of epithelial cells

PLoS One. 2023 Nov 27;18(11):e0291331. doi: 10.1371/journal.pone.0291331. eCollection 2023.

Abstract

B. parapertussis is one of the etiological agents of whooping cough. Once inhaled, the bacteria bind to the respiratory epithelium and start the infection. Little is known about this first step of host colonization and the role of the human airway epithelial barrier on B. parapertussis infection. We here investigated the outcome of the interaction of B. parapertussis with a polarized monolayer of respiratory epithelial cells. Our results show that B. parapertussis preferentially attaches to the intercellular boundaries, and causes the disruption of the tight junction integrity through the action of adenylate cyclase toxin (CyaA). We further found evidence indicating that this disruption enables the bacterial access to components of the basolateral membrane of epithelial cells to which B. parapertussis efficiently attaches and gains access to the intracellular location, where it can survive and eventually spread back into the extracellular environment. Altogether, these results suggest that the adenylate cyclase toxin enables B. parapertussis to overcome the epithelial barrier and eventually establish a niche of persistence within the respiratory epithelial cells.

MeSH terms

  • Adenylate Cyclase Toxin / metabolism
  • Bordetella parapertussis* / metabolism
  • Bordetella pertussis / metabolism
  • Epithelial Cells / metabolism
  • Humans
  • Intracellular Space / metabolism
  • Whooping Cough* / microbiology

Substances

  • Adenylate Cyclase Toxin

Grants and funding

This work was supported by the National Agency for Scientific and Technological Promotion (ANPCyT-MINCyT) [PICT 2016 2363 to MER, PICT-2019-04296 to JPG] and La Plata National University (www.unlp.edu.ar) [Grant 11/X811 to MER]. JPG MC, JAH, and YAL are members of the Scientific Career of CONICET. CMB is a doctoral fellow of CONICET. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.