Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 33436239Publication DOI: 10.1016/j.carbpol.2020.117475Journal NLM ID: 8307156Publisher: Elsevier
Correspondence: huangdi
nankai.edu.cn; fenglu63
nankai.edu.cn
Institutions: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin, PR China, TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin, PR China
Extraintestinal pathogenic Escherichia coli (ExPEC) has presented a major clinical infection emerged in the past decades. O-polysaccharide (OPS)-based glycoconjugate vaccines produced using the bacterial glycosylation machinery can be utilized to confer protection against such infection. However, constructing a low-cost microbial cell factory for high-efficient production of OPS-based glycoconjugate vaccines remains challenging. Here, we engineered a glyco-optimized chassis strain by reprogramming metabolic network. The yield was enhanced to 38.6 mg L-1, the highest level reported so far. MS analysis showed that designed glycosylation sequon was modified by target polysaccharide with high glycosylation efficiency of 90.7 % and 76.7 % for CTB-O5 and CTB-O7, respectively. The glycoconjugate vaccines purified from this biosystem elicited a marked increase in protection against ExPEC infection in mouse model, compared to a non-optimized system. The glyco-optimized platform established here is broadly suitable for polysaccharide-based conjugate production against ExPEC and other surface-polysaccharide-producing pathogens.
O-polysaccharide, glycoconjugate vaccine, ExPEC, glyco-optimized chassis strain, glycosylation efficiency, sugar to protein ratio
Structure type: suggested polymer biological repeating unit
Location inside paper: Fig. S1(C), O7
Compound class: O-polysaccharide, core oligosaccharide, O-antigen
Contained glycoepitopes: IEDB_130701,IEDB_136044,IEDB_136105,IEDB_137472,IEDB_141794,IEDB_141807,IEDB_144983,IEDB_150899,IEDB_151531,IEDB_152206,IEDB_190606,IEDB_225177,IEDB_885823,IEDB_983930,SB_137,SB_165,SB_166,SB_187,SB_195,SB_29,SB_44,SB_67,SB_7,SB_72,SB_88
Methods: SDS-PAGE, sugar analysis, ELISA, Western blotting, genetic methods, LC-MS, cloning, immunization, RP-LC-MS/MS
Related record ID(s): 10870
NCBI Taxonomy refs (TaxIDs): 2162916Reference(s) to other database(s): GTC:G47971KQ, GlycomeDB:
27141
Show glycosyltransferases
There is only one chemically distinct structure:
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