Research Papers:

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

Dianpeng Han, Yu Liu, Jingjing Li, Chenghua Liu, Yaping Gao, Jiannan Feng, Huizhe Lu _ and Guang Yang

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Oncotarget. 2018; 9:26086-26095. https://doi.org/10.18632/oncotarget.25441

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Dianpeng Han1,2, Yu Liu1,2, Jingjing Li3, Chenghua Liu1,2, Yaping Gao1,2, Jiannan Feng1,2, Huizhe Lu4 and Guang Yang1,2

1Beijing Institute of Basic Medical Sciences, Beijing, China

2State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China

3Henan University School of Basic Medical Science, Kaifeng, China

4Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, China

Correspondence to:

Huizhe Lu, email: [email protected]

Guang Yang, email: [email protected]

Keywords: macrolides resistant; rplV; repeat insertion; Staphylococcus aureus

Received: February 09, 2018     Accepted: April 28, 2018     Published: May 25, 2018


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.

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