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Molecular Pathogenesis

Contribution of a Response Regulator to the Virulence of Streptococcus pneumoniae Is Strain Dependent

Clare E. Blue, Tim. J. Mitchell
Clare E. Blue
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom
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Tim. J. Mitchell
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom
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  • For correspondence: t.mitchell@bio.gla.ac.uk
DOI: 10.1128/IAI.71.8.4405-4413.2003
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  • FIG. 1.
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    FIG. 1.

    Gene organization around the TCS09 locus. The rr and hk genes make up S. pneumoniae tcs09. An erythromycin resistance cassette was inserted to replace the rr09 gene. R9F and R9R, primers used to create and confirm mutations within the rr09 gene. Downstream of the tcs09 locus is a conserved hypothetical protein (open arrow) and a gene, zmpB, encoding a putative zinc metalloprotease (3, 23). Immediately upstream lies msrA, encoding a methionine sulfoxide reductase, also important in virulence (35). Primer pairs P1-P2, P3-P4, and P1-P4 were used to confirm that the organization of genes surrounding tcs09 was conserved in the two strains used in this study. The diagram is not drawn to scale.

  • FIG. 2.
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    FIG. 2.

    Survival of mice following intraperitoneal infection with 105 CFU of wild-type or mutant bacteria. (a) Strains on a D39 background. ▪, wild-type strain D39; □, the Δrr09 mutant. P < 0.05 for survival time with the Δrr09 mutant compared to that with the D39 parental strain. (b) Strains on a 0100993 background. •, wild-type strain 0100993; ○, the Δ488 mutant. No difference in survival was seen between animals challenged with the Δ488 mutant and the 0100993 parental strain.

  • FIG. 3.
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    FIG. 3.

    Intranasal challenge with 107 CFU on a D39 background. (a) Survival; (b) bacteremia. ▪, wild-type strain D39; □, the Δrr09 mutant. P < 0.05 for survival and for bacteremia at all time points after 0 h. In panel b, error bars represent SEMs; dashed line represents the limit of detection (log10 1.92 CFU ml−1).

  • FIG. 4.
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    FIG. 4.

    Intranasal challenge with 107 CFU on a 0100993 background. (a) Survival; (b) bacteremia. •, wild-type 0100993; ○, the Δ488 mutant. P < 0.05 for survival and for bacteremia at all time points after 24 h. In panel b, error bars represent SEMs; dashed line represents the limit of detection (log10 1.92 CFU ml−1).

  • FIG. 5.
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    FIG. 5.

    Bacterial loads in the lung tissue 24 and 48 h following intranasal infection with 107 CFU. (a) Strains on a D39 background. Filled bars, wild-type D39; hatched bars, the Δrr09 mutant. P < 0.05 for wild-type versus mutant lung counts at both time points. (b) Strains on a 0100993 background. Filled bars, wild-type 0100993; hatched bars, the Δ488 mutant. No differences were found between wild-type and mutant lung counts at either time point studied. Values are geometric means ± SEMs. The dashed line represents the limit of detection.

  • FIG. 6.
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    FIG. 6.

    Intravenous challenge with 106 CFU on a D39 background. (a) Survival; (b) bacteremia. ▪, wild-type D39; □, the Δrr09 mutant. P < 0.05 for survival and for bacteremia at all time points after 0 h. In panel b, error bars represent SEMs; dashed line represents the limit of detection (log10 1.92 CFU ml−1).

  • FIG. 7.
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    FIG. 7.

    Intravenous challenge with 106 CFU on a 0100993 background. (a) Survival; (b) bacteremia. •, wild-type 0100993; ○, the Δ488 mutant. No differences were seen in survival or level of bacteremia between mice infected with 0100993 or the Δ488 mutant at any of the time points studied. In panel b, error bars represent SEMs; dashed line represents the limit of detection (log10 1.92 CFU ml−1).

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Contribution of a Response Regulator to the Virulence of Streptococcus pneumoniae Is Strain Dependent
Clare E. Blue, Tim. J. Mitchell
Infection and Immunity Jul 2003, 71 (8) 4405-4413; DOI: 10.1128/IAI.71.8.4405-4413.2003

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Contribution of a Response Regulator to the Virulence of Streptococcus pneumoniae Is Strain Dependent
Clare E. Blue, Tim. J. Mitchell
Infection and Immunity Jul 2003, 71 (8) 4405-4413; DOI: 10.1128/IAI.71.8.4405-4413.2003
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KEYWORDS

Streptococcus pneumoniae

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