Bordetella pertussis is the bacterium responsible for pertussis, commonly known as whooping cough. This highly contagious respiratory illness can be particularly severe, especially in infants. Pertussis toxin (PT), a powerful substance produced by the bacterium, plays a central role in causing the distinctive and harmful symptoms associated with whooping cough. It acts as a key virulence factor, allowing the bacteria to establish and prolong infection in the human respiratory tract.
What is Pertussis Toxin?
Pertussis toxin is a protein exotoxin, secreted by the Bordetella pertussis bacterium. It possesses a complex A-B toxin structure, consisting of an active (A) component and a binding (B) component that work together to exert the toxin’s effects within host cells.
The A component, the S1 subunit, holds the enzymatic activity responsible for the toxin’s harmful actions. The B component is a pentameric ring made up of five subunits: S2, S3, two copies of S4, and S5. These B subunits bind to specific molecules on the surface of host cells, facilitating the entry of the active S1 subunit into the cell. This organized structure allows the toxin to target and disrupt cellular processes effectively.
How the Toxin Disrupts Body Functions
Once inside the host cell, pertussis toxin modifies G-proteins through a process called ADP-ribosylation. G-proteins act as cellular “on/off switches,” regulating a wide array of cell functions, including immune responses and cell signaling pathways. The toxin targets and modifies the alpha subunits of inhibitory G proteins, such as Gαi and Gαo.
This modification prevents the G-proteins from interacting normally with their associated receptors on the cell membrane. As a result, they become locked in an inactive state, unable to inhibit adenylyl cyclase, an enzyme that produces cyclic AMP (cAMP). This leads to an uncontrolled increase in intracellular cAMP levels. The elevated cAMP disrupts normal cellular communication and function, particularly within immune cells like macrophages, lymphocytes, and neutrophils. This interference impairs the body’s ability to mount an effective immune response against the bacterial infection.
The Toxin’s Role in Whooping Cough
The cellular disruptions caused by pertussis toxin directly contribute to the severe symptoms and progression of whooping cough. The toxin’s interference with G-protein signaling impairs the normal function of immune cells. For instance, it can lead to lymphocytosis, an abnormal increase in lymphocytes in the bloodstream, while preventing these immune cells from migrating to the site of infection in the respiratory tract.
Beyond immune suppression, pertussis toxin also damages the cilia, which are tiny, hair-like structures lining the respiratory tract that normally help clear mucus and debris. This ciliary damage, combined with inflammation and swelling, leads to the characteristic severe, prolonged coughing fits known as paroxysms. These intense coughing bouts can be followed by a high-pitched “whoop” as the person struggles to inhale. The toxin’s ability to weaken the body’s defenses and directly harm respiratory tissues prolongs the infection and contributes to complications like vomiting after coughing, difficulty breathing, and in severe cases, pneumonia or seizures. The toxin plays a role in sustaining the infection throughout its typical stages, from an initial cold-like phase to severe coughing fits, before gradual recovery.
Protecting Against Pertussis Toxin
Vaccination is the primary method for protecting against pertussis toxin and preventing whooping cough. Modern pertussis vaccines, such as DTaP for children and Tdap for adolescents and adults, are “acellular” vaccines. These vaccines do not contain whole, inactivated bacteria but instead include purified components of Bordetella pertussis, with a key ingredient being a detoxified form of pertussis toxin, known as pertussis toxoid.
This pertussis toxoid has been chemically treated to neutralize its harmful effects while retaining its ability to stimulate an immune response. When administered, the toxoid prompts the immune system to produce specific antibodies that can recognize and neutralize the actual pertussis toxin if an individual is exposed to the B. pertussis bacterium. This antibody response helps prevent the toxin from disrupting cellular functions and causing severe disease. Vaccination is recommended to prevent whooping cough, reduce its severity, and protect vulnerable populations, especially infants, through community immunity.