Monday, October 30, 2006
Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae
Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by point mutations in the quinolone resistance-determining regions of gyrA and pare. 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.
Streptococcus pneumoniae causes otitis media, baceremia, and meningitis and is a leading cause of community-acquired bacterial pneumonia worldwide. Pneumococcal infections are commonly treated with [beta]-lactams, macrolides, and, increasingly, fluoroquinolones. Pneumococcal resistance to each of these drug classes has increased in recent years (1,2). Initially, antimicrobial resistance in a pathogen may come at a cost: modifications that allow survival in the presence of antimicrobial drugs may render the pathogen less efficient at host infection, even in the absence of the antimicrobial agent (3). Little is known about the fitness of antimicrobial-resistant S. pneumoniae (4-8). The emergence of quinolone-resistant S. pneumoniae (QRSP) appears to be more dependent on fluoroquinolone selection of de novo spontaneous point mutations in the quinolone resistance-determining regions (QRDRs) of the topoisomerase genes gyrA and parC than on clonal dissemination (9-13). However, some studies reported occurrences of clonal relatedness among QRSP (11,14-16).
Streptococcus pneumoniae causes otitis media, baceremia, and meningitis and is a leading cause of community-acquired bacterial pneumonia worldwide. Pneumococcal infections are commonly treated with [beta]-lactams, macrolides, and, increasingly, fluoroquinolones. Pneumococcal resistance to each of these drug classes has increased in recent years (1,2). Initially, antimicrobial resistance in a pathogen may come at a cost: modifications that allow survival in the presence of antimicrobial drugs may render the pathogen less efficient at host infection, even in the absence of the antimicrobial agent (3). Little is known about the fitness of antimicrobial-resistant S. pneumoniae (4-8). The emergence of quinolone-resistant S. pneumoniae (QRSP) appears to be more dependent on fluoroquinolone selection of de novo spontaneous point mutations in the quinolone resistance-determining regions (QRDRs) of the topoisomerase genes gyrA and parC than on clonal dissemination (9-13). However, some studies reported occurrences of clonal relatedness among QRSP (11,14-16).
# posted by Medical Information : 1:42 AM
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