Pertussis toxin is a potent substance produced by Bordetella pertussis, the bacterium causing whooping cough (pertussis). This toxin plays a significant role in how the bacterium establishes infection and causes severe symptoms. It is a major factor in the progression of this highly contagious respiratory illness.
The Toxin’s Structure and Function
Pertussis toxin is a complex AB5-type exotoxin, secreted by the bacterium. It consists of six subunits, labeled S1 through S5, with two copies of the S4 subunit.
The S1 subunit is the “A” component, possessing the toxin’s enzymatic activity. The “B” component, a pentameric ring of S2, S3, two S4, and S5 subunits, binds to specific molecules on human cell surfaces.
Once attached, the toxin enters the cell. The S1 subunit then performs ADP-ribosylation, transferring an ADP-ribose molecule onto G proteins.
How Pertussis Toxin Affects the Body
Pertussis toxin primarily targets inhibitory G proteins (Gi proteins) within human cells. Normally, Gi proteins regulate various cellular processes by relaying signals. When ADP-ribosylated, Gi proteins are locked in an inactive state, preventing the normal shutdown of signaling pathways and leading to an overproduction of cyclic AMP (cAMP).
Increased cAMP levels have widespread consequences. It impairs immune cell function, inhibiting phagocytes from engulfing bacteria. It also interferes with chemokine production, which attracts immune cells like neutrophils and macrophages. Consequently, the immune system’s initial response is weakened, allowing Bordetella pertussis to evade early defenses.
A notable systemic effect is lymphocytosis, an abnormal increase of lymphocytes in the bloodstream. This occurs because the toxin disrupts lymphocyte trafficking, preventing their return to lymph nodes and other tissues. The toxin can also cross the blood-brain barrier, potentially leading to neurological complications.
These widespread cellular disruptions contribute to the prolonged and severe nature of whooping cough.
Role in Whooping Cough Pathogenesis
Pertussis toxin is a major virulence factor for Bordetella pertussis, enabling the bacterium to cause disease. The toxin’s inhibition of Gi proteins and elevated cAMP levels directly contribute to whooping cough symptoms and progression. By suppressing the early immune response, the toxin allows bacteria to colonize and persist in the respiratory tract.
Disrupted immune cell function, including impaired neutrophil and macrophage migration, means the body struggles to contain the infection. This immune evasion allows bacteria to multiply and establish a foothold, leading to prolonged airway inflammation. Persistent irritation and inflammation, exacerbated by the toxin, contribute to the severe, uncontrollable coughing fits characteristic of whooping cough.
These intense coughs can lead to complications like broken ribs, pneumonia, and brain damage from lack of oxygen. The toxin’s systemic effects, such as lymphocytosis, reflect its widespread impact. This disruption contributes to the illness’s overall severity and protracted course.
Without pertussis toxin, Bordetella pertussis would be far less effective at causing such a debilitating infection, underscoring its central role in whooping cough pathogenesis.
Pertussis Toxin in Vaccines
Pertussis toxin is a significant component in modern acellular pertussis vaccines (DTaP for children, Tdap for adolescents and adults). Because the unmodified toxin causes disease, it cannot be used directly.
Instead, it undergoes detoxification, becoming a “toxoid.” This neutralizes the toxin’s harmful enzymatic activity while preserving its structure for immune recognition.
When administered, the detoxified pertussis toxoid safely stimulates antibody production against the harmful toxin. These antibodies can then neutralize pertussis toxin if a vaccinated individual is exposed to Bordetella pertussis.
This protective immune response prevents severe whooping cough. The inclusion of pertussis toxoid is a cornerstone of vaccine effectiveness, targeting one of the bacterium’s most potent virulence factors and reducing disease severity.