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Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.

Forbes ML, Horsey E, Hiller NL, Buchinsky FJ, Hayes JD, Compliment JM, Hillman T, Ezzo S, Shen K, Keefe R, Barbadora K, Post JC, Hu FZ, Ehrlich GD - PLoS ONE (2008)

Bottom Line: Highly significant variation was observed among the strains in their ability to cause disease and moribundity.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of America.

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 findings: For 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/significance: As 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.

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Severity of otoscopic change.Scatter plot illustrating the maximal otologic score for each animal inoculated with each of the S. pneumoniae strains, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 9.56e−5 and Kruskal-Wallis p-value =  0.00118). Colors represent different serotypes, and shades of the same color different strains of the same serotype or in the case of BS68(9) two cohorts from different experiments. NA: non applicable.
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pone-0001969-g003: Severity of otoscopic change.Scatter plot illustrating the maximal otologic score for each animal inoculated with each of the S. pneumoniae strains, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 9.56e−5 and Kruskal-Wallis p-value =  0.00118). Colors represent different serotypes, and shades of the same color different strains of the same serotype or in the case of BS68(9) two cohorts from different experiments. NA: non applicable.

Mentions: We also analyzed the maximal otologic score for each animal as a measure for the severity of local disease (where scores of 0 and 1 were considered to be the same since they are hard to discern) (Fig. 3). The mean score for maximal otologic disease among the fourteen strains was 2.26±0.87. Mean scores for individual strains ranged from 1.3 for strains BS71(3) and BS72(23) to 2.83 for strains BS75(19), BS437(9), BS73(6), BS69(14), and TIGR4(4) (Table 3). Statistical analysis of this data set showed a significant difference amongst the strains (ANOVA p-value = 9.56e−5, and Kruskal-Wallis p-value =  0.00118) (Table 2). Further analysis of all the strain pairs using Tukey HSD, showed that the strains with the least severe otoscopic disease BS71(3) and BS72(23) differed significantly from BS437(9), BS69(14), BS73(6), BS75-19, and TIGR4(4). There was a significant correlation between days to onset of otoscopic disease and the maximal otoscopic score (Spearman's rank correlation rho = −0.311 with p-value = 0.009).


Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.

Forbes ML, Horsey E, Hiller NL, Buchinsky FJ, Hayes JD, Compliment JM, Hillman T, Ezzo S, Shen K, Keefe R, Barbadora K, Post JC, Hu FZ, Ehrlich GD - PLoS ONE (2008)

Severity of otoscopic change.Scatter plot illustrating the maximal otologic score for each animal inoculated with each of the S. pneumoniae strains, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 9.56e−5 and Kruskal-Wallis p-value =  0.00118). Colors represent different serotypes, and shades of the same color different strains of the same serotype or in the case of BS68(9) two cohorts from different experiments. NA: non applicable.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279396&req=5

pone-0001969-g003: Severity of otoscopic change.Scatter plot illustrating the maximal otologic score for each animal inoculated with each of the S. pneumoniae strains, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 9.56e−5 and Kruskal-Wallis p-value =  0.00118). Colors represent different serotypes, and shades of the same color different strains of the same serotype or in the case of BS68(9) two cohorts from different experiments. NA: non applicable.
Mentions: We also analyzed the maximal otologic score for each animal as a measure for the severity of local disease (where scores of 0 and 1 were considered to be the same since they are hard to discern) (Fig. 3). The mean score for maximal otologic disease among the fourteen strains was 2.26±0.87. Mean scores for individual strains ranged from 1.3 for strains BS71(3) and BS72(23) to 2.83 for strains BS75(19), BS437(9), BS73(6), BS69(14), and TIGR4(4) (Table 3). Statistical analysis of this data set showed a significant difference amongst the strains (ANOVA p-value = 9.56e−5, and Kruskal-Wallis p-value =  0.00118) (Table 2). Further analysis of all the strain pairs using Tukey HSD, showed that the strains with the least severe otoscopic disease BS71(3) and BS72(23) differed significantly from BS437(9), BS69(14), BS73(6), BS75-19, and TIGR4(4). There was a significant correlation between days to onset of otoscopic disease and the maximal otoscopic score (Spearman's rank correlation rho = −0.311 with p-value = 0.009).

Bottom Line: Highly significant variation was observed among the strains in their ability to cause disease and moribundity.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of America.

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 findings: For 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/significance: As 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.

Show MeSH
Related in: MedlinePlus