title: Mutations in 23S rRNA account for intrinsic resistance to macrolides in Mycoplasma hominis and Mycoplasma fermentans and for acquired resistance to macrolides in M. hominis.
abstract: The mechanisms of intrinsic resistance of Mycoplasma hominis to 14- and 15-membered macrolides were investigated in comparison with those of M. pneumoniae, which is naturally susceptible to macrolides. Radiolabeled erythromycin was not accumulated by M. hominis PG21, but addition of an ABC transporter inhibitor increased the level of erythromycin uptake more than two times, suggesting the existence of an active efflux process. The affinity of [(14)C]erythromycin to ribosomes isolated from M. hominis was dramatically reduced relative to that to ribosomes isolated from M. pneumoniae. The nucleotide sequences of 23S rRNA of both ribosomal operons rrnA and rrnB and ribosomal proteins L4 and L22 of M. hominis were obtained. Compared to the sequence of M. pneumoniae, M. hominis harbored a G2057A transition in its 23S rRNA sequence, as did M. fermentans, another mycoplasma that is erythromycin resistant. An additional C2610U change was also found in the sequence of M. hominis. Moreover, two M. hominis clinical isolates with acquired resistance to 16-membered macrolides were examined for mutations in domain II and domain V of 23S rRNA and in ribosomal proteins L4 and L22. Compared to the sequence of reference strain PG21, one isolate harbored a A2059G transition and a C2611U transition in one of the two rrn operons, while the other one was mutated only at position 2059, also on the same operon. No mutation was found in the two ribosomal protein sequences. Overall, the present study is an exhaustive characterization of the intrinsic resistance of M. hominis to 14- and 15-membered macrolides and the first description of mycoplasma clinical isolates resistant to macrolide, lincosamide, and streptogramin antibiotics harboring a mutation at position 2611 in the 23S rRNA.
authors.affiliation: Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Pereyre
authors.forename: P
authors.initials: P
authors.lastname: Gonzalez
authors.forename: B
authors.initials: B
authors.lastname: De Barbeyrac
authors.forename: A
authors.initials: A
authors.lastname: Darnige
authors.forename: H
authors.initials: H
authors.lastname: Renaudin
authors.forename: A
authors.initials: A
authors.lastname: Charron
authors.forename: S
authors.initials: S
authors.lastname: Raherison
authors.forename: C
authors.initials: C
authors.lastname: Bébéar
authors.forename: C M
authors.initials: CM
authors.lastname: Bébéar
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology; D020459:Genes, rRNA / Q000235:genetics; D006801:Humans; D015570:Josamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D016858:Mycoplasma fermentans / Q000187:drug effects* / Q000235:genetics; D019535:Mycoplasma hominis / Q000187:drug effects* / Q000235:genetics; D009690:Nucleic Acid Conformation; D012338:RNA, Ribosomal, 23S / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D012338:RNA, Ribosomal, 23S; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C056368:ribosomal protein L4; C067169:RPL22 protein, human; D004917:Erythromycin; D015570:Josamycin