title: Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations.
abstract: Clonal emergence of group A streptococci (GAS) with reduced susceptibility to fluoroquinolones (FQs) has been increasingly reported. Non-susceptibility is associated with various point mutations in the target-encoding genes and has only been described in a few emm types. We used a well-characterised GAS clinical paediatric collection from Brussels (Belgium) and Brasília (Brazil) to analyse the molecular basis of FQ non-susceptibility. GAS strains were tested for ciprofloxacin susceptibility and were screened for mutations in DNA gyrase- and topoisomerase IV-encoding genes. Genetic relationships between the different emm types were assessed by phylogenetic analysis of the whole surface-exposed part of the M protein. A high proportion (22.5%) of ciprofloxacin-non-susceptible isolates (minimal inhibitory concentration > or = 2mg/L) was found among the Belgian strains. They belonged mostly to emm type 6 (87%). In Brazil, 6% of the isolates, belonging to seven distantly related emm types, were non-susceptible. Our phylogenetic analysis showed that non-susceptibility may arise in various genetic backgrounds. Sequence comparison of the quinolone resistance-determining regions (QRDRs) of the ParC- and ParE-encoding genes from susceptible and non-susceptible isolates revealed that most of the mutations were found in both classes of isolates, indicating an emm type-linked polymorphism. In conclusion, we observed a clonal spreading of non-susceptible emm type 6 GAS strains in Brussels and a polyclonal distribution of non-susceptible isolates in Brazil. All the Brazilian and Belgian emm type 6 strains displayed a S79A/F mutation in parC that convincingly explains the non-susceptible phenotype.
authors.affiliation: Laboratoire de Génétique et Physiologie Bactérienne, Institut de Biologie et de Médecine Moléculaires (IBMM), Faculté des Sciences, Université Libre de Bruxelles, 12 Rue des Professeurs Jeener et Brachet, 6041 Gosselies, Belgium. psmeeste@ulb.ac.be
authors.forename: Pierre Robert
authors.initials: PR
authors.lastname: Smeesters
authors.forename: Anne
authors.initials: A
authors.lastname: Vergison
authors.forename: Dioclécio Campos
authors.initials: DC
authors.lastname: Junior
authors.forename: Laurence
authors.initials: L
authors.lastname: Van Melderen
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D001530:Belgium; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D027081:DNA Gyrase / Q000235:genetics; D004252:DNA Mutational Analysis; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D024841:Fluoroquinolones; C014689:streptococcal M protein; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase