title: Modulation of ccrAB Expression and SCCmec Excision by an Inverted Repeat Element and SarS in Methicillin-Resistant Staphylococcus aureus.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious human pathogen that can cause a broad spectrum of infections. MRSA strains are resistant to almost the entire family of β-lactam antibiotics due to the acquisition of staphylococcal cassette chromosome mec (SCCmec). The chromosome cassette recombinases A and B, encoded by ccrAB genes located on SCCmec, play a key role in the excision of SCCmec. Studies have shown that ccrAB genes are expressed in only a minority of cells, suggesting the involvement of a subtle regulatory mechanism in ccrAB expression which has not been uncovered. Here, we found that an inverted repeat (IR) element, existing extensively and conservatively within the ccrAB promoter of different SCCmec types, played a repressive role in ccrAB expression and SCCmec excision in MRSA strain N315. Replacement of the IR sequence led to a significant increase in ccrAB expression and curing of SCCmec from strain N315 cells. In addition, we identified the transcriptional regulator SarS using DNA-affinity chromatography and further demonstrated that SarS can bind to the IR sequence and upregulate ccrAB expression and SCCmec excision. These findings reveal a molecular mechanism regulating ccrAB expression and SCCmec excision and may provide mechanic insights into the lateral transfer of SCCmec and spread of antibiotic resistance in S. aureus.
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Ma
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China sunb@ustc.edu.cn.
authors.forename: Baolin
authors.initials: B
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D022761:Gene Transfer, Horizontal; D055029:Inverted Repeat Sequences; D008712:Methicillin / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D045522:Recombinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D045522:Recombinases; D012097:Repressor Proteins; C476149:SarS protein, Staphylococcus aureus; D008712:Methicillin