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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids
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Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids

机译:金黄色葡萄球菌对甲氧西林的抗药性需要糖基化壁壁chochochoic酸

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摘要

Staphylococcus aureus peptidoglycan (PG) is densely functionalized with anionic polymers called wall teichoic acids (WTAs). These polymers contain three tailoring modifications: D-alanylation, α-O-GlcNAcylation, and β-O-GlcNAcylation. Here we describe the discovery and biochemical characterization of a unique glycosyltrans-ferase, TarS, that attaches β-O-GlcNAc (β-O-/V-acetyl-D-glucosamine) residues to S. aureus WTAs. We report that methicillin resistant S. aureus (MRSA) is sensitized to β-lactams upon tarS deletion. Unlike strains completely lacking WTAs, which are also sensitive to β-lactams, ΔtarS strains have no growth or cell division defects. Because neither α-O-GlcNAc nor β-O-Glucose modifications can confer resistance, the resistance phenotype requires a highly specific chemical modification of the WTA backbone, β-O-GlcNAc residues. These data suggest β-O-GlcNAcylated WTAs scaffold factors required for MRS A resistance. The β-O-GlcNAc transferase identified here, TarS, is a unique target for antimicrobials that sensitize MRSA to β-lactams.
机译:金黄色葡萄球菌肽聚糖(PG)被称为壁壁chochochoic酸(WTA)的阴离子聚合物稠密地官能化。这些聚合物包含三个定制修饰:D-丙氨酰化,α-O-GlcNAcylation和β-O-GlcNAcylation。在这里,我们描述了独特的糖基转移酶TarS的发现和生化特性,该酶将β-O-GlcNAc(β-O-/ V-乙酰基-D-葡萄糖胺)残基附着到金黄色葡萄球菌WTA。我们报告说,在tarS缺失后,耐甲氧西林的金黄色葡萄球菌(MRSA)对β-内酰胺敏感。与完全缺乏WTA的菌株(对β-内酰胺类同样敏感)不同,ΔtarS菌株没有生长或细胞分裂缺陷。因为α-O-GlcNAc修饰和β-O-葡萄糖修饰都不能赋予抗性,所以抗性表型要求WTA主链的高特异性化学修饰,即β-O-GlcNAc残基。这些数据表明MRS A耐药性需要β-O-GlcNAcylatedWTAs支架因子。此处鉴定的β-O-GlcNAc转移酶TarS是使MRSA对β-内酰胺敏感的抗微生物药物的独特靶标。

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  • 作者单位

    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;

    Cellular and Molecular Microbiology Section, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Elfriede-Aulhorn-Strasse 6, D-72076 Turbingen, Germany;

    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115;

    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;

    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;

    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;

    Cellular and Molecular Microbiology Section, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Elfriede-Aulhorn-Strasse 6, D-72076 Turbingen, Germany;

    Cellular and Molecular Microbiology Section, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Elfriede-Aulhorn-Strasse 6, D-72076 Turbingen, Germany;

    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115;

    Cellular and Molecular Microbiology Section, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Elfriede-Aulhorn-Strasse 6, D-72076 Turbingen, Germany;

    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    PBP2A; antibiotic resistance; beta lactam potentiation; murein; WTA glycosylation;

    机译:PBP2A;抗生素耐药性;β内酰胺增强;壁素WTA糖基化;

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