title: Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae.
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.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama 35249, USA.
authors.forename: Crystal N
authors.initials: CN
authors.lastname: Johnson
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.forename: William H
authors.initials: WH
authors.lastname: Benjamin
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hollingshead
authors.forename: Ken B
authors.initials: KB
authors.lastname: Waites
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D009154:Mutation; D009305:Nasopharynx / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase