Mechanisms of macrolide resistance in Ureaplasma urealyticum: a study on collection and clinical strains

Ureaplasma urealyticum is considered as a species which is intrinsically sensitive to macrolides (MIC less than 1 microgram/ml). Nevertheless, some of the strains recently isolated in our laboratories showed moderate to high levels of resistance (MICs ranging from 2 micrograms/ml to 100 micrograms/ml). In particular, a strain (CT28) isolated from a patient with nongonococcal urethritis long treated with erythromycin revealed a MIC greater than 100 micrograms/ml for this antibiotic. In order to investigate the mechanisms of resistance, strain CT28 and ten clinical and laboratory U. urealyticum strains were compared for the sensitivity to six antibiotics including three macrolides. Moreover the amount of macrolide uptake and the specific antibiotic binding to ribosomes were studied. Strain CT28 was resistant to josamycin, erythromycin, roxithromycin, lincomycin and clindamycin but sensitive to minocycline. When compared to a sensitive strain, strain CT28 showed a six-fold reduction in intracellular macrolide influx and accumulation and a reduction in antibiotic binding to ribosomes. The mechanisms implicated in these differences may be important for macrolide resistance in U. urealyticum.