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Published on: January 22, 2021
Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae
Crystal N Johnson1, David E Briles, William H Benjamin
1University 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.
Insights
Quinolone-resistant Streptococcus pneumoniae (QRSP) with common clinical mutations show reduced fitness in colonization and infection models. However, laboratory-derived QRSP mutants exhibit varied fitness, impacting their ability to cause disease.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Fluoroquinolone resistance in Streptococcus pneumoniae is primarily driven by mutations in gyrA and parC genes.
- Antimicrobial resistance mutations can negatively impact bacterial fitness.
Purpose of the Study:
- To investigate the fitness of quinolone-resistant Streptococcus pneumoniae (QRSP) strains.
- To compare the relative growth efficiencies of isogenic QRSP double mutants with their susceptible parent strain.
Main Methods:
- Utilized murine nasopharyngeal colonization and pneumonia models.
- Compared the competitive fitness of two isogenic QRSP double mutants against the fluoroquinolone-susceptible parent strain EF3030.
Main Results:
- QRSP strains with GyrA:Ser81Phe and ParC:Ser79Phe mutations (frequent in clinical isolates) exhibited poor competitive colonization and lung infection compared to EF3030.
- These clinical QRSP mutants could still efficiently cause lung infection independently.
- QRSP strains with GyrA:Ser81Phe and ParC:Ser79Tyr mutations (frequent in laboratory isolates) showed reduced nasal colonization but comparable lung infection capabilities to EF3030.
Conclusions:
- The fitness of quinolone-resistant Streptococcus pneumoniae varies depending on specific mutation profiles.
- Clinical QRSP mutations may confer a fitness cost, while laboratory-derived mutations show more varied fitness impacts.
- Understanding QRSP fitness is crucial for predicting their epidemiological behavior and treatment outcomes.
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