A novel 23S rRNA mutation in Propionibacterium acnes confers resistance to 14-membered macrolides

Nakase, Keisuke; Nakaminami, Hidemasa; Takenaka, Yuko; Hayashi, Nobuyuki; Kawashima, Makoto; Noguchi, Norihisa

doi:10.1016/j.jgar.2016.05.005

Cited by 11 publications

(12 citation statements)

References 5 publications

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“…When the MIC for the resistant mutants were measured, the most frequently detected A2058G mutants showed high‐level resistance to both macrolides and clindamycin, the A2059G mutants showed high‐level macrolide resistance but low‐level clindamycin resistance, and the C2611G mutants showed high‐level resistance to only clarithromycin. These results are similar to those of previous reports on clinical isolates with the 23S rRNA mutation …”

Section: Resultssupporting

confidence: 93%

“…The macrolide resistance determinants of the macrolide‐resistant mutants were identified by DNA sequencing of the 23S rRNA, ribosomal L4 gene rplD and the L10 protein gene rplJ , following the methods described by Nakase et al …”

Section: Methodsmentioning

confidence: 99%

“…Macrolide resistance in P. acnes includes macrolide–lincosamide–streptogramin B resistance, because it shows cross‐resistance to clindamycin (lincosamides) and streptogramin B. The 23S rRNA mutations at bases 2057–2059 and 2611, which is the target site of macrolides, predominate over 90% of resistant strains . Resistant strains with these mutations show different susceptibilities to macrolides and clindamycin, depending on the mutation point.…”

Section: Introductionmentioning

confidence: 99%

“…The 23S rRNA mutations at bases 2057-2059 and 2611, which is the target site of macrolides, predominate over 90% of resistant strains. [8][9][10] Resistant strains with these mutations show different susceptibilities to macrolides and clindamycin, depending on the mutation point. Strains with an A2058G mutation exhibit high-level resistance to macrolides and clindamycin while strains with a C2611G mutation exhibit high-level resistance to only 14-membered macrolides.…”

Section: Introductionmentioning

confidence: 99%

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Long‐term administration of oral macrolides for acne treatment increases macrolide‐resistant Propionibacterium acnes

Nakase

Okamoto

Aoki

et al. 2017

The Journal of Dermatology

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Macrolide-resistant Propionibacterium acnes are frequently isolated from patients with acne vulgaris, and the most resistant isolates (>90% resistance) have the 23S rRNA mutation. An increase in resistant P. acnes with this mutation is thought to be caused by the inappropriate use of antimicrobials. Therefore, we studied the mutation frequency of macrolide resistance in P. acnes in vitro. When P. acnes mutants were exposed to clarithromycin after being incubated in broth without antimicrobials, resistant mutants with the 23S rRNA mutation were not isolated. However, the mutants were obtained at the frequency of 10 after being pre-incubated with 0.03 μg/mL of antimicrobials. This is the estimated epidermal concentration of clarithromycin after p.o. administration. The resistant mutants had the 23S rRNA mutations A2058G, A2059G and C2611G. When pre-incubated with clarithromycin, C2611G mutants which showed resistance to clarithromycin were obtained 32.1% more often than pre-incubated with clindamycin (P < 0.01). By contrast, when pre-incubated with clindamycin, A2058G mutants, which show high-level resistance to both clarithromycin and clindamycin, were more frequently obtained than pre-incubated with clarithromycin (87.5%, P < 0.01). No difference in the isolation rate of A2059G mutants, which show high-level resistance to macrolides but low-level resistance to clindamycin, was found with either treatment. These results indicate the possibility that long-term use of oral macrolides for acne treatment facilitate the increase of macrolide-resistant P. acnes.

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Section: Resultssupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long‐term administration of oral macrolides for acne treatment increases macrolide‐resistant Propionibacterium acnes

Nakase

Okamoto

Aoki

et al. 2017

The Journal of Dermatology

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“…Alternatively, mutations might be present in the 23S rRNA gene peptidyl transferase coding region. Sequence variations in this gene causing MLS B resistance in P. acnes have been described at positions 2057–2059 and 2611 . MLS B resistance levels among P. acnes strains differ according to the specific 23S rRNA residue affected, with the A2058G mutation in particular resulting in high‐level clindamycin resistance.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial susceptibility and phylogenetic analysis ofPropionibacterium acnesisolated from acne patients in Japan between 2013 and 2015

Nakase

Hayashi

Akiyama

et al. 2017

The Journal of Dermatology

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The prevalence of antimicrobial-resistant Propionibacterium acnes strains isolated from acne patients has been increasing in Japan. Here, to estimate the current resistance rate, we tested antimicrobial susceptibility among P. acnes from acne patients having visited a specialized dermatology clinic between 2013 and 2015. Rates of resistance to macrolides and clindamycin were 44.3 (31/70) and 38.6% (27/70), respectively. erm(X), which confers high-level clindamycin resistance (minimum inhibitory concentration ≥256 μg/mL), was detected in six isolates, whereas no resistance determinants were identified in eight strains showing high-level resistance to clindamycin. Using single-locus sequence typing, the P. acnes isolates were classified into five clades (A, E, F, H and K), with all high-level clindamycin-resistant strains lacking known clindamycin resistance determinants being grouped together (in clade F). P. acnes isolates from patients previously treated with macrolides and clindamycin showed a macrolide resistance rate (55.3%) significantly higher than that of those from patients not having received these treatments (21.7%, P < 0.05). Furthermore, strains of clade F, which were very rarely isolated from healthy individuals, were more frequently recovered from patients with severe acne (40.0%) than those with mild acne (23.3%). Our data showed an increase in macrolide-resistant P. acnes prevalence in Japan due to the use of antimicrobial agents for acne treatment. Furthermore, we identified strains of specific phylogenetic groups frequently associated with severe acne patients.

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Current Macrolide Antibiotics and Their Mechanisms of Action

Lohsen

Stephens

2019

Antibiotic Drug Resistance

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A novel 23S rRNA mutation in Propionibacterium acnes confers resistance to 14-membered macrolides

Cited by 11 publications

References 5 publications

Long‐term administration of oral macrolides for acne treatment increases macrolide‐resistant Propionibacterium acnes

Long‐term administration of oral macrolides for acne treatment increases macrolide‐resistant Propionibacterium acnes

Antimicrobial susceptibility and phylogenetic analysis ofPropionibacterium acnesisolated from acne patients in Japan between 2013 and 2015

Current Macrolide Antibiotics and Their Mechanisms of Action

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