Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides.,Nature Chemical Biology

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Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides.
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2019-04-01 , DOI: 10.1038/s41589-019-0251-4
Rebecca J Edgar _{1,

2} , Vincent P van Hensbergen ₃ , Alessandro Ruda ₄ , Andrew G Turner ₅ , Pan Deng ₆ , Yoann Le Breton _{7,

8} , Najib M El-Sayed _{7,

9} , Ashton T Belew _{7,

9} , Kevin S McIver ₇ , Alastair G McEwan ₅ , Andrew J Morris ₆ , Gérard Lambeau ₁₀ , Mark J Walker ₅ , Jeffrey S Rush ₁ , Konstantin V Korotkov ₁ , Göran Widmalm ₄ , Nina M van Sorge ₃ , Natalia Korotkova ₁

Affiliation

Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
Callaghan Innovation, Gracefield, Lower Hutt, New Zealand.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden.
Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Division of Cardiovascular Medicine and the Gill Heart Institute, University of Kentucky, Lexington, KY, USA.
Department of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne Sophia Antipolis, France.

Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A2. Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.

中文翻译：

发现链球菌鼠李糖多糖上的磷酸甘油酯修饰。

革兰氏阳性细菌表面的细胞壁糖聚合物是细菌生理学和感染生物学的基础。在这里，我们在两个独立的转座子文库筛选中鉴定了化脓性链球菌A类碳水化合物（GAC）生物合成簇中的一个基因gacH，以赋予其对锌的抗性和对人类IIA型分泌磷脂酶A2的敏感性。随后的GacH细胞外结构域的结构和系统发育分析表明，GacH代表了另一类甘油磷酸转移酶。我们检测到GAC中存在磷酸甘油酯，以及来自变形链球菌的血清型c碳水化合物，这取决于各个gacH同源物的存在。最后，GAC的核磁共振分析证实磷酸甘油酯在C6羟基处约占GAC N-乙酰氨基葡糖侧链的25％。这种先前无法识别的结构修饰会影响宿主与病原体的相互作用，并对疫苗设计产生影响。

更新日期：2019-05-16

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