Pertussis Toxin Promotes Pulmonary Hypertension in an Infant Mouse Model of Bordetella pertussis Infection

Area of Science:

• Pediatric infectious diseases
• Cardiovascular research
• Bacterial pathogenesis

Background:

• Pertussis (whooping cough), caused by Bordetella pertussis, is reemerging globally.
• Infants are particularly susceptible to severe manifestations, including pulmonary hypertension (PH), a significant cause of mortality.
• The underlying molecular mechanisms of B. pertussis-induced PH remain poorly understood, hindering effective treatment development.

Purpose of the Study:

• To investigate the age-dependent mechanisms of Bordetella pertussis-induced pulmonary hypertension (PH).
• To determine the role of pertussis toxin in the development of PH during infection.
• To explore potential therapeutic strategies targeting pertussis toxin for PH and severe pertussis.

Main Methods:

• Utilized infant and adult mouse models to study pertussis infection.
• Assessed pulmonary hypertension using Fulton index, right heart catheterization, and Doppler echocardiography.
• Analyzed the correlation between bacterial pertussis toxin expression and PH severity.

Main Results:

• Bordetella pertussis-induced pulmonary hypertension (PH) demonstrated significant age-related differences in severity.
• The development and severity of PH were directly dependent on the expression of pertussis toxin by the bacteria.
• Pertussis toxin was identified as a key mediator in the pathogenesis of B. pertussis-induced PH.

Conclusions:

• Pertussis toxin plays a critical role in the age-dependent development of pulmonary hypertension during Bordetella pertussis infection.
• Pertussis toxin-targeting therapies show promise for ameliorating PH and reducing mortality in infants with severe pertussis.
• Further research into pertussis toxin's mechanisms is warranted for developing effective treatments against severe pertussis and its complications.