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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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Related in: MedlinePlus

Percentage recovery units (PRUs: CFUs recovered from nasal wash or lung homogenate divided by CFUs originally used to infect mice and multiplied by 106) for competitive pneumonia infection with Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A), EF3030 and the Phe/Tyr mutant (B), and noncompetitive pneumonia with EF3030, Phe/Phe, and Phe/Tyr (C). Lines connect data from the same mouse. Bars indicate median PRUs. NP, nasopharynx. p values were calculated by the Wilcoxon matched-pairs signed-rank test (A and B) and the Mann-Whitney unpaired 2-tailed test (C).
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Figure 3: Percentage recovery units (PRUs: CFUs recovered from nasal wash or lung homogenate divided by CFUs originally used to infect mice and multiplied by 106) for competitive pneumonia infection with Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A), EF3030 and the Phe/Tyr mutant (B), and noncompetitive pneumonia with EF3030, Phe/Phe, and Phe/Tyr (C). Lines connect data from the same mouse. Bars indicate median PRUs. NP, nasopharynx. p values were calculated by the Wilcoxon matched-pairs signed-rank test (A and B) and the Mann-Whitney unpaired 2-tailed test (C).

Mentions: Of the 23 mice infected with approximately equal amounts (104 CFUs of each strain or 106 CFUs of each strain) of EF3030 and Phe/Phe, all 23 were colonized nasopharyngeally, and lung infection developed in 13 of 23. EF3030 outcompeted Phe/Phe in both the nasopharynx (p<0.001) and the lungs (p<0.001) (Figure 3A).


Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae.

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

Percentage recovery units (PRUs: CFUs recovered from nasal wash or lung homogenate divided by CFUs originally used to infect mice and multiplied by 106) for competitive pneumonia infection with Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A), EF3030 and the Phe/Tyr mutant (B), and noncompetitive pneumonia with EF3030, Phe/Phe, and Phe/Tyr (C). Lines connect data from the same mouse. Bars indicate median PRUs. NP, nasopharynx. p values were calculated by the Wilcoxon matched-pairs signed-rank test (A and B) and the Mann-Whitney unpaired 2-tailed test (C).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Percentage recovery units (PRUs: CFUs recovered from nasal wash or lung homogenate divided by CFUs originally used to infect mice and multiplied by 106) for competitive pneumonia infection with Streptococcus pneumoniae EF3030 and the Phe/Phe mutant (A), EF3030 and the Phe/Tyr mutant (B), and noncompetitive pneumonia with EF3030, Phe/Phe, and Phe/Tyr (C). Lines connect data from the same mouse. Bars indicate median PRUs. NP, nasopharynx. p values were calculated by the Wilcoxon matched-pairs signed-rank test (A and B) and the Mann-Whitney unpaired 2-tailed test (C).
Mentions: Of the 23 mice infected with approximately equal amounts (104 CFUs of each strain or 106 CFUs of each strain) of EF3030 and Phe/Phe, all 23 were colonized nasopharyngeally, and lung infection developed in 13 of 23. EF3030 outcompeted Phe/Phe in both the nasopharynx (p<0.001) and the lungs (p<0.001) (Figure 3A).

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