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Clostridioides difficile cd2775 Encodes a Unique Mannosyl-1-Phosphotransferase for Polysaccharide II Biosynthesis.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2020-02-20 , DOI: 10.1021/acsinfecdis.9b00494
Zhongrui Ma 1 , Gao-Lan Zhang 1 , Madhusudhan Reddy Gadi 1 , Yuxi Guo 1 , Peng Wang 1 , Lei Li 1
Affiliation  

Clostridioides difficile (C. difficile) is the leading cause of antibiotic-induced bacterial colitis and life-threatening diarrhea worldwide. The commonly existing anionic polysaccharide II (PSII) is responsible for protein anchoring involved in colonization, and the gene cd2775 located in its biosynthesis gene cluster is essential for bacterial growth. Herein, we demonstrated that cd2775 encodes a novel mannosyl-1-phosphotransferase (ManPT) responsible for the phosphorylation of PSII. Unlike typical mannosyltransferases, CD2775 transfers mannose-α1-phosphate instead of mannose from guanosine 5'-diphospho-d-mannose to disaccharide acceptors, forming a unique mannose-α1-phosphate-6-glucose linkage. The enzyme was overexpressed in E. coli and purified for biochemical characterization and substrate specificity study. It is found that CD2775 possesses a strict acceptor specificity toward Glc-β1,3-GalNAc-diphospho-lipids but extreme promiscuity toward various sugar donors. This is the first report of a ManPT in all living systems. Given its essentiality in C. difficile growth, CD2775 can be a promising target for therapeutics development.

中文翻译:

艰难梭菌cd2775编码独特的甘露糖基-1-磷酸转移酶,用于多糖II的生物合成。

艰难梭菌(C. difficile)是抗生素引起的细菌性结肠炎和危及生命的腹泻的主要原因。常见的阴离子多糖II(PSII)负责定居过程中的蛋白质锚定,位于其生物合成基因簇中的cd2775基因对于细菌的生长至关重要。在这里,我们证明了cd2775编码负责PSII磷酸化的新型甘露糖基1-磷酸转移酶(ManPT)。与典型的甘露糖基转移酶不同,CD2775将甘露糖-α1-磷酸而不是甘露糖从鸟苷5'-二磷酸-d-甘露糖转移至二糖受体,形成独特的甘露糖-α1-磷酸-6-葡萄糖键。该酶在大肠杆菌中过表达,并纯化用于生化表征和底物特异性研究。发现CD2775对Glc-β1,3-GalNAc-二磷酸脂质具有严格的受体特异性,而对各种糖供体具有极端的混杂性。这是ManPT在所有生命系统中的首次报告。鉴于其在艰难梭菌生长中的重要性,CD2775可以成为治疗学发展的有希望的靶标。
更新日期:2020-02-19
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