title: Characterization of Enterococcus faecium with macrolide resistance and reduced susceptibility to quinupristin/dalfopristin in a Japanese hospital: detection of extensive diversity in erm(B)-regulator regions.
abstract: Cross-resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics is mainly mediated by the erm (erythromycin ribosome methylation) genes that encode 23S rRNA methylases in enterococi, and various mechanisms are involved in the streptogramin B resistance. Prevalence of MLSB resistance and its genetic mechanisms were analyzed for a total of 159 strains of Enterococcus faecium isolated from clinical specimens in a university hospital in Japan from 1997 to 2006. Resistance to erythromycin (EM) and clindamycin was detected in 88.1% and 89.9% of all the strains examined, respectively, and expression of resistance was totally constitutive. Although none of the strain was resistant to quinupristin/dalfopristin (Q/D), 28 strains (17.6%) showed intermediate resistance to Q/D (MIC: 2 μg/ml). The erm(B) gene was detected in 139 strains (87.4%), and msrC was found in all the strains examined, whereas no other known MLSB resistance genes were identified. The erm(B) regulator region (RR) containing a coding region of the leader peptide was classified into 13 genetic variations (L1-L3, M, S1-S7, D, and R genotypes) in 56 strains. However, no relatedness was identified between the erm(B) RR genotype and EM resistance, or reduced susceptibility to Q/D, although most of Q/D-intermediate strains were assigned to the L1, L2, and S1 genotypes. Q/D-intermediate strains were classified into five multiple-locus variable-number tandem-repeat analysis (MLVA) types, including four types of clonal complex (CC)-C1, five sequence types (STs), including four STs of CC-17, and several resistance gene/virulence factor profiles. The present study revealed the occurrence of Q/D-intermediate E. faecium, which are composed of heterogeneous strains in Japan, and more genetic diversity in the erm(B) RRs than those reported previously.
authors: Department of Hygiene, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors: Nayuta
authors: N
authors: Isogai
authors: Noriko
authors: N
authors: Urushibara
authors: Mitsuyo
authors: M
authors: Kawaguchiya
authors: Souvik
authors: S
authors: Ghosh
authors: Keisuke
authors: K
authors: Suzaki
authors: Naoki
authors: N
authors: Watanabe
authors: Dianelys
authors: D
authors: Quiñones
authors: Nobumichi
authors: N
authors: Kobayashi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D016984:Enterococcus faecium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D014644:Genetic Variation; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007564:Japan; D018942:Macrolides / Q000494:pharmacology*; D008780:Methyltransferases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014769:Virginiamycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018942:Macrolides; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D008780:Methyltransferases