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Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae.

Johnson CN, Briles DE, Benjamin WH, Hollingshead SK, Waites KB - Emerging Infect. Dis. (2005)

Bottom Line: Antimicrobial resistance mutations in housekeeping genes often decrease fitness of microorganisms.The strain containing the GyrA: Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal colonization in competitive or noncompetitive lung infections.However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030.

View Article: PubMed Central - PubMed

Affiliation: University of Alabama at Birmingham, Birmingham, Alabama 35249, USA.

ABSTRACT
Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by point mutations in the quinolone resistance-determining regions of gyrA and parC. Antimicrobial resistance mutations in housekeeping genes often decrease fitness of microorganisms. To investigate the fitness of quinolone-resistant S. pneumoniae (QRSP), the relative growth efficiencies of 2 isogenic QRSP double mutants were compared with that of their fluoroquinolone-susceptible parent, EF3030, by using murine nasopharyngeal colonization and pneumonia models. Strains containing the GyrA: Ser81Phe, ParC: Ser79Phe double mutations, which are frequently seen in clinical QRSP, competed poorly with EF3030 in competitive colonization or competitive lung infections. However, they efficiently produced lung infection even in the absence of EF3030. The strain containing the GyrA: Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal colonization in competitive or noncompetitive lung infections. However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030.

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In vitro competition between Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A) and between EF3030 and the Phe/Tyr mutant (B) in liquid medium (broth). Bars indicate medians. Lines connect strains competing in the same broth. p values were calculated by the Wilcoxon matched-pairs signed-rank test.
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Figure 1: In vitro competition between Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A) and between EF3030 and the Phe/Tyr mutant (B) in liquid medium (broth). Bars indicate medians. Lines connect strains competing in the same broth. p values were calculated by the Wilcoxon matched-pairs signed-rank test.

Mentions: Overall, EF3030 underwent more generations per 6-hour in vitro growth period than either Phe/Phe (p<0.016) (Figure 1A) or Phe/Tyr (p<0.007) (Figure 1B). Of 10 mice intranasally infected with approximately equal amounts (106 CFUs) of EF3030 and Phe/Phe, 8 were colonized. Among these 8 mice, EF3030 outcompeted Phe/Phe (p<0.023) (Figure 2A). Of 10 mice intranasally infected with approximately equal amounts of EF3030 and Phe/Tyr, 8 were colonized. Among these 8 mice, EF3030 outcompeted Phe/Tyr (p<0.008) (Figure 2B).


Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae.

Johnson CN, Briles DE, Benjamin WH, Hollingshead SK, Waites KB - Emerging Infect. Dis. (2005)

In vitro competition between Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A) and between EF3030 and the Phe/Tyr mutant (B) in liquid medium (broth). Bars indicate medians. Lines connect strains competing in the same broth. p values were calculated by the Wilcoxon matched-pairs signed-rank test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367570&req=5

Figure 1: In vitro competition between Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A) and between EF3030 and the Phe/Tyr mutant (B) in liquid medium (broth). Bars indicate medians. Lines connect strains competing in the same broth. p values were calculated by the Wilcoxon matched-pairs signed-rank test.
Mentions: Overall, EF3030 underwent more generations per 6-hour in vitro growth period than either Phe/Phe (p<0.016) (Figure 1A) or Phe/Tyr (p<0.007) (Figure 1B). Of 10 mice intranasally infected with approximately equal amounts (106 CFUs) of EF3030 and Phe/Phe, 8 were colonized. Among these 8 mice, EF3030 outcompeted Phe/Phe (p<0.023) (Figure 2A). Of 10 mice intranasally infected with approximately equal amounts of EF3030 and Phe/Tyr, 8 were colonized. Among these 8 mice, EF3030 outcompeted Phe/Tyr (p<0.008) (Figure 2B).

Bottom Line: Antimicrobial resistance mutations in housekeeping genes often decrease fitness of microorganisms.The strain containing the GyrA: Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal colonization in competitive or noncompetitive lung infections.However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030.

View Article: PubMed Central - PubMed

Affiliation: University of Alabama at Birmingham, Birmingham, Alabama 35249, USA.

ABSTRACT
Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by point mutations in the quinolone resistance-determining regions of gyrA and parC. Antimicrobial resistance mutations in housekeeping genes often decrease fitness of microorganisms. To investigate the fitness of quinolone-resistant S. pneumoniae (QRSP), the relative growth efficiencies of 2 isogenic QRSP double mutants were compared with that of their fluoroquinolone-susceptible parent, EF3030, by using murine nasopharyngeal colonization and pneumonia models. Strains containing the GyrA: Ser81Phe, ParC: Ser79Phe double mutations, which are frequently seen in clinical QRSP, competed poorly with EF3030 in competitive colonization or competitive lung infections. However, they efficiently produced lung infection even in the absence of EF3030. The strain containing the GyrA: Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal colonization in competitive or noncompetitive lung infections. However, the strain was equally able to cause competitive or noncompetitive lung infections as well as EF3030.

Show MeSH
Related in: MedlinePlus