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Oncotarget. 2018 May 25;9(40):26086-26095. doi: 10.18632/oncotarget.25441. eCollection 2018 May 25.

Twenty-seven-nucleotide repeat insertion in the rplV gene confers specific resistance to macrolide antibiotics in Staphylococcus aureus.

Han D1,2, Liu Y1,2, Li J3, Liu C1,2, Gao Y1,2, Feng J1,2, Lu H4, Yang G1,2.

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Beijing Institute of Basic Medical Sciences, Beijing, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
Henan University School of Basic Medical Science, Kaifeng, China.
Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, China.


Macrolide antibiotics are used for treatment of soft-tissue infection caused by Staphylococcus aureus in humans. However, infections with S. aureus are increasingly difficult to treat owing to the emergence and rapid spread of multiple-drug resistant S. aureus. Resistance to macrolide in S. aureus is mostly due to the modification of 23 S rRNA by methylases encoded by erm genes. Here, we have identified that a 27-nucleotide repeat sequence insertion in the rplV gene induced a specific resistance to macrolide antibiotics. An erythromycin-resistant strain, 8325ER+, was screened by resistance to erythromycin from the macrolide-sensitive strain 8325-4. Comparative genome sequencing analysis showed that 8325ER+ contained a 27-nt repeat sequence insertion in the rplV gene that encodes the ribosomal protein L22, when compared to its parent strain. The 27-nt repeat sequence led to an insertion of 9 amino acids in L22, which had been identified to reduce the sensitivity to erythromycin and other macrolide antibiotics. Moreover, we show that the ectopic expression of the mutated rplV gene containing the 27-nt repeat sequence insertion in several susceptible strains specifically conferred resistance to macrolide antibiotics. Our findings present a potential mechanism of resistance to macrolide antibiotics in S. aureus.


Staphylococcus aureus; macrolides resistant; repeat insertion; rplV

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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