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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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Related in: MedlinePlus

Days to moribund condition.Scatter plot illustrating the timing to the development of a moribund condition for each of the fourteen pneumococcal strains in the chinchilla model of otitis media. No moribundity was observed in the cohorts inoculated with TIGR4(4) or the unencapsulated strain BS293. Each triangle represents a single animal. 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-g004: Days to moribund condition.Scatter plot illustrating the timing to the development of a moribund condition for each of the fourteen pneumococcal strains in the chinchilla model of otitis media. No moribundity was observed in the cohorts inoculated with TIGR4(4) or the unencapsulated strain BS293. Each triangle represents a single animal. 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: Animals that were inoculated with BS71(3) and BS72(23) rapidly displayed signs of systemic moribundity, which effected our ability to gauge the development of otoscopic disease past day 2 (Fig. 4). Importantly, many strains show otoscopic changes by day 1 or 2 (Fig. 2), demonstrating that systemic moribundity by day 2 does not prohibit the development of otoscopic signs, as is most evident for strain BS68(9), which showed high otologic scores by day 2 (Fig. 3 and 4). Nonetheless, to account for the affect of the loss of animals infected with systemically virulent strains on the strain's otoscopic scores, we performed Kaplan-Meier Survival Probability Estimates. These results confirmed that days to onset of otoscopic disease were significantly different between the strains (the log-rank test for days to onset of moderate or worse otologic disease had a p-value = 6.446e−12, 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)

Days to moribund condition.Scatter plot illustrating the timing to the development of a moribund condition for each of the fourteen pneumococcal strains in the chinchilla model of otitis media. No moribundity was observed in the cohorts inoculated with TIGR4(4) or the unencapsulated strain BS293. Each triangle represents a single animal. 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-g004: Days to moribund condition.Scatter plot illustrating the timing to the development of a moribund condition for each of the fourteen pneumococcal strains in the chinchilla model of otitis media. No moribundity was observed in the cohorts inoculated with TIGR4(4) or the unencapsulated strain BS293. Each triangle represents a single animal. 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: Animals that were inoculated with BS71(3) and BS72(23) rapidly displayed signs of systemic moribundity, which effected our ability to gauge the development of otoscopic disease past day 2 (Fig. 4). Importantly, many strains show otoscopic changes by day 1 or 2 (Fig. 2), demonstrating that systemic moribundity by day 2 does not prohibit the development of otoscopic signs, as is most evident for strain BS68(9), which showed high otologic scores by day 2 (Fig. 3 and 4). Nonetheless, to account for the affect of the loss of animals infected with systemically virulent strains on the strain's otoscopic scores, we performed Kaplan-Meier Survival Probability Estimates. These results confirmed that days to onset of otoscopic disease were significantly different between the strains (the log-rank test for days to onset of moderate or worse otologic disease had a p-value = 6.446e−12, 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