# Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis

## TL;DR

This paper explains how pertussis toxin disrupts host cell signaling through ADP-ribosylation and other mechanisms to aid bacterial infection.

## Contribution

The paper clarifies the dual functionality of pertussis toxin, distinguishing cAMP-dependent and cAMP-independent effects.

## Key findings

- Pertussis toxin's A subunit ADP-ribosylates Gαi proteins, leading to increased cAMP levels.
- The B oligomer of pertussis toxin can trigger signaling independently of ADP-ribosylation.
- Pertussis toxin works with adenylate cyclase toxin to subvert immune defenses.

## Abstract

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gαi), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium’s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx’s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit’s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx’s dual functionality, distinguishing its Gi protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive Gi signaling and the interplay between PTx and ACT shape host–pathogen interaction in pertussis pathogenesis.