Molecular Epidemiology of Bordetella pertussis

Abstract

Bordetella pertussis is the causative agent of whooping cough, a highly contagious infection of the upper respiratory tract that can lead to particularly severe disease in infants and young children, including death. A whole cell vaccine was introduced in the 1940s leading to a rapid decline in the number of cases; however adverse events from the vaccine led to the development and release of a safer acellular vaccine in the 1990s. Since the introduction of the acellular vaccine, pertussis cases began to rise. The past few years have seen a particularly large resurgence in cases; in 2012 the number of reported cases in the United States was the highest since 1955. Reasons for this resurgence are not entirely clear. As a large proportion of cases are in fully vaccinated individuals, we hypothesized that interactions with host microbiota through coaggregation interactions may play a role in who gets infected. We further hypothesized that vaccination selected for B. pertussis strains without the antigens included in the vaccine. To explore the ability of B. pertussis to coaggregate with common commensals of the nasopharynx we developed a high-throughput method for its detection. I applied this method to screen for coaggregation between 10 B. pertussis strains with 20 nasopharygeal commensal strains. We also used whole genome sequencing and phylogenetic analysis of 100 B. pertussis isolates randomly selected from 8 vaccination time periods to test whether vaccination produced a bottleneck in the B. pertussis genome. There was apparent coaggregation between B. pertussis and strains of H. influenzae, P. aeriginosa, S. aureus, S. pyogenes, and S. pneumoniae; however visual examination using the FlowCam™ runs and confocal microscopy suggested induction of autoaggregation in B. pertussis by S. aureus and P. aeruginosa, and no interaction between B. pertussis and the other strains. By inducing autoaggregation in B. pertussis, S. aureus and P. aeriginosa may be able to prevent B. pertussis from colonizing the host. Analysis of the genetic sequence data suggests that pre-vaccine era isolates are distinct from post-vaccination strains (p<0.0001) and that B. pertussis underwent a bottleneck.