Hypervirulent serotype 1 pneumococci display high levels of nasal shedding and rapid onward transmission

Abstract

OBJECTIVES: Streptococcus pneumoniae serotype 1 (S1) is a major cause of invasive pneumococcal disease. Despite its high attack rate, S1 exhibits a low carriage prevalence within the population, which raises questions about the relationship between nasopharyngeal carriage and transmission of hypervirulent strains between individuals. We compared the transmission dynamics of S1 to serotypes 2 (S2) and 3 (S3) using a novel model of transmission in adolescent mice. METHODS: Donor "index" mice were intranasally infected with S1, S2, S3 or isogenic pneumolysin-deficient mutants and co-housed with naïve recipient "contact" mice. Three days later, all mice were infected with influenza A virus (IAV). Pneumococcal transmission was analysed during colonisation alone and co-infection with IAV by quantification of the nasal shedding and nasopharyngeal bacterial density in both index and contact mice. The role of the polysaccharide capsule and toxin pneumolysin, as well as biofilm production in shedding and transmission, and the host nasopharyngeal immune response, were investigated. RESULTS: We show that S1 was shed at significantly greater levels than S2 and S3 in index mice, which led to significantly higher shedding and transmission rates in contact mice. S1 produced less biofilm and a thick capsule that promoted its increased shedding and transmission. Interestingly, pneumococcal acquisition led to pneumolysin-dependant macrophage recruitment in the nasopharynx of contact mice. CONCLUSION: Our results show that rapid and high transmission rate of serotype 1 is a key factor for its success in disseminating quickly within the population and causing outbreaks.