Abstract
Pertussis (“whooping cough”) is a re-emerging disease with increasing incidence among fully vaccinated individuals. We explored the genetic diversity of five Bordetella pertussis proteins used to generate the subunit vaccine across ancestral and newly emergent strains using immunoinformatics and evolutionary selection measurements. The five subunits of pertussis toxin (Ptx1–Ptx5) were highly conserved with regard to sequence, predicted structure, predicted antigenicity, and were under purifying selection. In contrast, the adhesin proteins pertactin (Prn) and filamentous hemagglutinin (FHA) were under statistically significant (p < 0.01) diversifying selection. Most heavily diversified sites of each protein fell within antigenic epitopes, and the functional adhesin motifs were conserved. Protein secondary structure was conserved despite sequence diversity for FHA but was changeable in Prn. These findings suggest that subunit vaccine-derived immunity does not impact Ptx1–Ptx5 but may apply evolutionary pressure to Prn and FHA to undergo diversifying selection. These findings offer further insight into the emergence of vaccine-resistant strains of B. pertussis.
Highlights
Bordetella pertussis is a human pathogen that causes respiratory illness across all age groups.Infants and children with pertussis experience an acute disease featuring a characteristic hacking, paroxysmal cough [1]
The protein sequences of the five pertussis toxin subunits were largely conserved across conserved across strains, suggesting that there is no evolutionary pressure to diversify acting on the strains, suggesting that there is no evolutionary pressure to diversify acting on the toxin
A statistically significant diversify selection is acting on Prn and filamentous hemagglutinin (FHA), indicating that B. pertussis benefits from changing such proteins in response to evolutionary pressure (Figure 2)
Summary
Bordetella pertussis is a human pathogen that causes respiratory illness across all age groups. Infants and children with pertussis experience an acute disease featuring a characteristic hacking, paroxysmal cough [1]. The illness is more extensive in infants and can lead to serious complications, including failure to thrive, apnea, cyanosis, pneumonia, respiratory failure, seizures, and death [2,3]. Infection in adolescents and adults may result in a prolonged cough and is occasionally associated with substantial morbidity [4]. The disease can feature fever and posttussive vomiting [1,4]. Mortality from pertussis most frequently occurs in infants and children, most notably those who are not vaccinated
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