Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model

Widespread use of conjugate vaccines against Streptococcus pneumoniae, by r educing carriage of S. pneumoniae serotypes included in the vaccine, may re sult in an increase in nasopharyngeal carriage of - and disease from - nonv accine serotypes of the same species. Mathematical models predict that the extent of such replacement will depend positively on the degree to which ca rriage of vaccine-type S. pneumoniae inhibits acquisition of nonvaccine-typ e pneumococci, and may depend negatively on the inhibition of vaccine-type pneumococci by nonvaccine-type pneumococci. We used a mouse model of intran asal carriage of pneumococci to test whether such inhibition occurs between different pneumococcal strains. Mice carrying a streptomycin-resistant der ivative of S. pneumoniae BG9163 (serotype 6B) as a resident strain showed r educed levels of colonization when challenged intranasally by optochin-resi stant derivatives of the same strain and of a serotype 23F pneumococcus, BG 8826. Inhibition could be overcome by increasing the dose of the challenge strain. Carriage of optochin-resistant BG9163 did not inhibit acquisition o f the streptomycin-resistant variant. Colonization by a challenge strain di d not significantly affect the level of colonization with the resident stra in. These results provide evidence that is consistent with several hitherto untested assumptions of mathematical models of serotype replacement and su ggest that a biological mechanism exists that could account for serotype re placement that is observed in clinical trials. The findings provide a basis for further studies of in vivo interactions between strains of S. pneumoni ae. Published by Elsevier Science Ltd.