Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model
Section snippets
Introduction and background
Conjugate vaccines against Streptococcus pneumoniae are currently in clinical trials [1], [2], [3], [4], [5]. These vaccines immunize against 7, 9, of the 90 known pneumococcal serotypes. Preliminary results from these ongoing trials in infants indicate that these vaccines are highly protective against invasive disease [1] and offer significant protection against pneumonia [1] and otitis media [1], [4], from the serotypes included in the vaccine. In addition, the vaccine offers partial
Bacterial strains
S. pneumoniae strains were antibiotic-resistant mutants isolated from strains BG9163 (serotype 6B) and BG8826 (23F) [12]. Optochin-resistant (Opt®) mutants were isolated on tryptic soy agar + 5% sheep’s blood plates (SBA) containing 5 mg/l optochin, and streptomycin-resistant (Str®) mutants were isolated on SBA plates containing 200 mg/l streptomycin. Isolates were restreaked on antibiotic plates and then grown to late log phase and plated on both antibiotic-containing and antibiotic-free
Carriage of a resident strain could inhibit colonization by a challenge strain
Fig. 2 shows the results of 7-day [Fig. 2(a)] and 14-day [Fig. 2(b)] experiments in which BG9163Str® was the resident strain and the otherwise isogenic BG9163Opt® was the challenge strain. Inocula were 7×104 cfu (resident strain) and 4×104 cfu (challenge strain) for the 7-day experiment, and 6×104 cfu (resident strain) and 4×104 cfu (challenge strain) for the 14-day experiment. Competition was observed both in the 7 and 14-day experiment. In the 7-day experiment, carriage of the resident strain
Discussion
The experiments reported here demonstrate that S. pneumoniae carried intranasally can interfere with nasal colonization by a second strain of S. pneumoniae to which the animal is exposed. The removal of this interference by reductions in carriage of vaccine-type S. pneumoniae provides a biological mechanism that could lead to serotype replacement following the introduction of a conjugate pneumococcal vaccine into a population.
As described in Section 1, mathematical models predict that the
Acknowledgements
The authors thank R. Malley for valuable discussions and helpful comments on a draft of the manuscript.
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