Clostridioides difficile cd2775 Encodes a Unique Mannosyl-1-Phosphotransferase for Polysaccharide II Biosynthesis.
ACS Infect Dis
; 6(4): 680-686, 2020 04 10.
Article
em En
| MEDLINE
| ID: mdl-32073825
ABSTRACT
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-ß1,3-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Fosfotransferases
/
Polissacarídeos Bacterianos
/
Clostridioides difficile
/
Manosiltransferases
Idioma:
En
Revista:
ACS Infect Dis
Ano de publicação:
2020
Tipo de documento:
Article