title: Propionibacterium acnes is developing gradual increase in resistance to oral tetracyclines.
abstract: Propionibacterium acnes is an anaerobic bacterium that causes deep infection in organs and prosthetic joints, in addition to acne vulgaris. Many tetracycline-resistant P. acnes strains have been isolated because oral tetracyclines are frequently used as an acne treatment against P. acnes. In this study, we found a novel tetracycline resistance mechanism in P. acnes. Three doxycycline-resistant (MIC: 16 µg ml-1) strains were isolated from 69 strains in acne patients in Japan between 2010 and 2011. Additionally, six insusceptible strains (MIC: 1-2 µg ml-1) that had reduced susceptibility compared to susceptible strains (MIC: ≤0.5 µg ml-1) were identified. All doxycycline-resistant strains had a G1036C mutation in the 16S rRNA gene in addition to an amino acid substitution in the ribosomal S10 protein encoded by rpsJ. By contrast, insusceptible strains had an amino acid substitution in the S10 protein but no mutation in the 16S rRNA. When the mutant with decreased susceptibility to doxycycline was obtained in vitro, only the mutated S10 protein was found (MIC: 4 µg ml-1), not the mutated 16S rRNA gene. This result shows that the S10 protein amino acid substitution contributes to reduced doxycycline susceptibility in P. acnes and suggests that tetracycline resistance is acquired through a 16S rRNA mutation after the S10 protein amino acid substitution causes reduced susceptibility.
authors.affiliation: Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakase
authors.affiliation: Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Nakaminami
authors.affiliation: Department of Dermatology, Tokyo Women's Medical University, 8-1 Kawadachou, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takenaka
authors.affiliation: Department of Dermatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Dermatology, Tokyo Women's Medical University, 8-1 Kawadachou, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Noguchi
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy / Q000382:microbiology; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D011425:Propionibacterium acnes / Q000187:drug effects / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013753:Tetracycline Resistance / Q000235:genetics*; D013754:Tetracyclines / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012336:RNA, Ribosomal, 16S; D013754:Tetracyclines