Studies on Prn variation in the mouse model and comparison with epidemiological data

Area of Science:

• Microbiology
• Immunology
• Evolutionary Biology

Background:

• Pertactin (Prn) is a key antigen in pertussis vaccines and a highly variable component of Bordetella pertussis.
• Vaccination with pertussis vaccines has been linked to shifts in predominant Prn types, suggesting vaccine-driven selection.
• Understanding these evolutionary dynamics is crucial for effective pertussis control.

Purpose of the Study:

• To investigate the evolutionary shifts in Bordetella pertussis pertactin (Prn) variants.
• To determine the fitness and colonization ability of different Prn variants in a host environment.
• To assess the utility of a mouse model for predicting changes in B. pertussis populations due to vaccination.

Main Methods:

• Comparative analysis of Prn types in clinical isolates over time.
• Construction and characterization of pertactin knock-out (Prn-ko) Bordetella pertussis mutants.
• Colonization studies in a mouse model using wild-type and mutant strains.
• Assessment of the impact of Prn and ptxP variations on colonization efficiency.

Main Results:

• Prn2 strains became predominant over Prn3 strains in vaccinated populations, indicating higher fitness.
• A Prn knock-out mutation significantly reduced bacterial colonization in the mouse trachea and lungs.
• Restoration of Prn significantly increased colonization compared to the knock-out mutant.
• Variations in the pertussis toxin promoter (ptxP) and Prn significantly influenced colonization ability.
• Colonization ability followed the order Prn1 > Prn2 ≈ Prn3, consistent with Prn1 predominance in unvaccinated populations.

Conclusions:

• Pertactin (Prn) plays a significant role in Bordetella pertussis colonization.
• Vaccine-driven selection has led to the emergence of fitter Prn variants (Prn2).
• The mouse model is a valuable tool for studying B. pertussis evolution and predicting population shifts in response to vaccination.