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.

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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