Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Associated disease: infection due to Clostridium difficile [ICD11:
XN0SE 
]
NCBI PubMed ID: 32073825Publication DOI: 10.1021/acsinfecdis.9b00494Journal NLM ID: 101654580Publisher: Washington, DC: American Chemical Society
Correspondence: lli22

gsu.edu
Institutions: Department of Chemistry , Georgia State University , 50 Decatur Street SE , Atlanta , Georgia 30303 , United States
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.
Substrate Specificity, CD2775, Clostridioides difficile, mannosyl-1-phosphotransferase, polysaccharide II
Structure type: suggested polymer biological repeating unit
Location inside paper: Fig.1A, C. difficile PSII repeating unit
Trivial name: PSII
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_130648,IEDB_130701,IEDB_137473,IEDB_142488,IEDB_144983,IEDB_144996,IEDB_144998,IEDB_146664,IEDB_152206,IEDB_189516,IEDB_241118,IEDB_983930,IEDB_983931,SB_192,SB_44,SB_67,SB_72
Methods: SDS-PAGE, kinetics assays, MALDI-MS, Western blotting, genetic methods, bioinformatic analysis, enzymatic synthesis, enzymatic assay
Related record ID(s): 3842
NCBI Taxonomy refs (TaxIDs): 1496Reference(s) to other database(s): GTC:G03661KQ
Show glycosyltransferases
There is only one chemically distinct structure: