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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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Rapidity of onset of moderate or worse systemic signs.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae strains to develop moderate or worse signs of systemic disease (score ≥2). Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 0.03 and Kruskal-Wallis p-value =  0.00118). Each triangle represents a single animal. Animals were not included that did not develop systemic disease before the end of the experiment. 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-g006: Rapidity of onset of moderate or worse systemic signs.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae strains to develop moderate or worse signs of systemic disease (score ≥2). Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 0.03 and Kruskal-Wallis p-value =  0.00118). Each triangle represents a single animal. Animals were not included that did not develop systemic disease before the end of the experiment. 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: The rapidity of the development of systemic signs across all fourteen strains produced a mean of 2.3 days±1.6 (Fig. 5). Table 1 describes the signs of systemic disease for which the animals were monitored, scores of 0.5 and above were considered, and animals that never developed systemic signs were excluded from the analysis. The means ranged from 1.5 days for strain BS71(3) and 1.58 days for BS68(9) to 4 days for BS290(9) (Table 3). Analysis of this data using ANOVA does not show any statistical significance amongst the strains, however, repetition of the analysis by the non-parametric Kruskal-Wallis test yielded a statistically significant p-value of 0.016 (Table 2). Since even healthy animals showed slightly lethargic behavior (score 0.5), as evident by the PBS control, we also analyzed the days to onset of moderate or worse systemic disease (only scores of 2 or above; thus all animals that did not develop at least moderate symptoms were excluded from this analysis) (Fig. 6). These values range from 1.5 days for BS71(3) to 4 days for BS437(9) (Table 3). The results showed a significant difference amongst all strains (ANOVA p-value = 0.03, Kruskal-Wallis test p-value =  0.001) (Table 2).


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)

Rapidity of onset of moderate or worse systemic signs.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae strains to develop moderate or worse signs of systemic disease (score ≥2). Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 0.03 and Kruskal-Wallis p-value =  0.00118). Each triangle represents a single animal. Animals were not included that did not develop systemic disease before the end of the experiment. 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-g006: Rapidity of onset of moderate or worse systemic signs.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae strains to develop moderate or worse signs of systemic disease (score ≥2). Statistical analysis of all the strains revealed a significant difference (ANOVA p-value = 0.03 and Kruskal-Wallis p-value =  0.00118). Each triangle represents a single animal. Animals were not included that did not develop systemic disease before the end of the experiment. 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: The rapidity of the development of systemic signs across all fourteen strains produced a mean of 2.3 days±1.6 (Fig. 5). Table 1 describes the signs of systemic disease for which the animals were monitored, scores of 0.5 and above were considered, and animals that never developed systemic signs were excluded from the analysis. The means ranged from 1.5 days for strain BS71(3) and 1.58 days for BS68(9) to 4 days for BS290(9) (Table 3). Analysis of this data using ANOVA does not show any statistical significance amongst the strains, however, repetition of the analysis by the non-parametric Kruskal-Wallis test yielded a statistically significant p-value of 0.016 (Table 2). Since even healthy animals showed slightly lethargic behavior (score 0.5), as evident by the PBS control, we also analyzed the days to onset of moderate or worse systemic disease (only scores of 2 or above; thus all animals that did not develop at least moderate symptoms were excluded from this analysis) (Fig. 6). These values range from 1.5 days for BS71(3) to 4 days for BS437(9) (Table 3). The results showed a significant difference amongst all strains (ANOVA p-value = 0.03, Kruskal-Wallis test p-value =  0.001) (Table 2).

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