Abstract

Background Streptococcus pneumoniae [Sp] infection is associated with local and systemic disease. Our current understanding of the differential contributions of genetic strain variation, serotype, and host response to disease phenotype is incomplete. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437); eleven of the thirteen strains have been genomically sequenced.Methodology/Principal FindingsFor each strain 100 colony forming units were injected bilaterally into the tympanic bullae of 6 young adult chinchillas under general anesthesia. All animals were examined daily for local and systemic disease by a blinded observer. Pneumatic otoscopy was used to evaluate local disease, and behavioral assessments served as the measure of systemic disease. Virulence scoring was performed using a 4-point scale to assess four clinical parameters [severity and rapidity of local disease onset; and severity and rapidity of systemic disease onset] during a 10-day evaluation period. Highly significant variation was observed among the strains in their ability to cause disease and moribundity.Conclusions/SignificanceAs expected, there was a significant correlation between the rapidity of systemic disease onset and severity of systemic disease; however, there was little correlation between the severity of otoscopic changes and severity of systemic disease. Importantly, it was observed that different strains of the same serotype produced as broad an array of disease phenotypes as did strains of different serotypes. We attribute these phenotypic differences among the strains to the high degree of genomic plasticity that we have previously documented.

Highlights

  • Otitis media (OM) is the most common malady for which children receive medical and surgical attention in the United States and Europe [1]

  • The means for the individual strain cohorts ranged from 1 day for strains BS291(9), BS75(19) and BS69(14) to 5.5 days for the unencapsulated strain BS293 and 4.6 for the capsulated strain BS74(6) (Fig. 2, Table 3)

  • Statistical analysis of all the strain pairs using Tukey HSD showed that unencapsulated BS293 and BS74(6), the strains with slowest onset of disease, differed significantly from strains BS290(9), BS291(9), BS436(9), BS437(9), BS68(9), BS69(14), BS70(11), BS73(6), BS75(19), and TIGR4(4)

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Summary

Introduction

Otitis media (OM) is the most common malady for which children receive medical and surgical attention in the United States and Europe [1]. OM has a wide range of clinical presentations [1] and if untreated can, in rare cases, lead to invasive and systemic disease states that are associated with moribundity. Other studies [16,17,18,19] have illuminated the complexities of pathogen-host interactions and provided evidence supporting the hypotheses that intrinsic pathogen virulence factors, as well as specific elements of the host response make independent contributions to the development of clinical phenotype providing potential targets for future therapies [20,21,22]. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437); eleven of the thirteen strains have been genomically sequenced

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