title: Fluoroquinolone resistance in atypical pneumococci and oral streptococci: evidence of horizontal gene transfer of fluoroquinolone resistance determinants from Streptococcus pneumoniae.
abstract: Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or =4.0 microg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the Streptococcus pneumoniae R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the "atypical" strains from pneumococci, and these strains clustered closely with S. mitis. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose QRDR sequences clustered with those of S. pneumoniae, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized Streptococcus mitis and Streptococcus oralis strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the "atypical" isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.
authors.affiliation: Department of Microbiology, Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong. margaretip@cuhk.edu.hk
authors.forename: Margaret
authors.initials: M
authors.lastname: Ip
authors.forename: Shirley S L
authors.initials: SS
authors.lastname: Chau
authors.forename: Fang
authors.initials: F
authors.lastname: Chi
authors.forename: Julian
authors.initials: J
authors.lastname: Tang
authors.forename: Paul K
authors.initials: PK
authors.lastname: Chan
mesh_terms: D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D022761:Gene Transfer, Horizontal; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D010802:Phylogeny; D013291:Streptococcus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D034361:Streptococcus mitis / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019533:Streptococcus oralis / Q000145:classification / Q000187:drug effects / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D024841:Fluoroquinolones