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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 otologic disease onset.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae clinical strains to develop moderate or worse (score ≥2) otologic disease, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference, the p-value for the ANOVA analysis was 9.6e−15, and for the Kruskal-Wallis test was 2.4e−5. Animals are not included that did not develop local disease before the end of the experiment or before reaching a moribund state. 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-g002: Rapidity of otologic disease onset.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae clinical strains to develop moderate or worse (score ≥2) otologic disease, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference, the p-value for the ANOVA analysis was 9.6e−15, and for the Kruskal-Wallis test was 2.4e−5. Animals are not included that did not develop local disease before the end of the experiment or before reaching a moribund state. 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: Across the fourteen strains the rapidity of otoscopic changes, defined as the days to the development of unambiguous otological signs (a score of 2 or above since differences between scores of 0 and 1 were difficult to discern, Table 1), produced a mean of 1.93 days±1.35 (standard deviation, SD) (Fig. 2). Note, that animals that never developed otoscopic disease (such as all PBS controls) were excluded from this set. An ANOVA analysis of the differences among the strains produced highly significant results (p-value = 9.6e−15) as did repetition of the analysis by the non-parametric Kruskal-Wallis test (p-value = 2.4e−5) (Table 2). 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). In addition unencapsulated BS293 also differed from BS71(3). Finally BS72(23) differed significantly from BS291(9), BS68(9), BS69(14), BS73(6) and BS75(19), the strains with the fastest onset of disease.


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 otologic disease onset.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae clinical strains to develop moderate or worse (score ≥2) otologic disease, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference, the p-value for the ANOVA analysis was 9.6e−15, and for the Kruskal-Wallis test was 2.4e−5. Animals are not included that did not develop local disease before the end of the experiment or before reaching a moribund state. 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-g002: Rapidity of otologic disease onset.Scatter plot showing the number of days it took for chinchillas inoculated with each of the S. pneumoniae clinical strains to develop moderate or worse (score ≥2) otologic disease, where each triangle represents a single animal. Statistical analysis of all the strains revealed a significant difference, the p-value for the ANOVA analysis was 9.6e−15, and for the Kruskal-Wallis test was 2.4e−5. Animals are not included that did not develop local disease before the end of the experiment or before reaching a moribund state. 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: Across the fourteen strains the rapidity of otoscopic changes, defined as the days to the development of unambiguous otological signs (a score of 2 or above since differences between scores of 0 and 1 were difficult to discern, Table 1), produced a mean of 1.93 days±1.35 (standard deviation, SD) (Fig. 2). Note, that animals that never developed otoscopic disease (such as all PBS controls) were excluded from this set. An ANOVA analysis of the differences among the strains produced highly significant results (p-value = 9.6e−15) as did repetition of the analysis by the non-parametric Kruskal-Wallis test (p-value = 2.4e−5) (Table 2). 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). In addition unencapsulated BS293 also differed from BS71(3). Finally BS72(23) differed significantly from BS291(9), BS68(9), BS69(14), BS73(6) and BS75(19), the strains with the fastest onset of disease.

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