Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: typhoid fever [ICD11:
1A07 
, ICD11:
XN4AM ];
infection due to Salmonella enterica [ICD11:
XN5VC ]
The structure was elucidated in this paperNCBI PubMed ID: 28167670Publication DOI: 10.1128/IAI.01021-16Journal NLM ID: 0246127Publisher: American Society for Microbiology
Correspondence: E.Kintz
uea.ac.uk; Marjan.vanderwoude
york.ac.uk
Institutions: Complex Carbohydrate Research Center, The University of Georgia, Athens, Georgia, USA, Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom, The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom
Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S Typhi genome. Strains were engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonellagtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.
Lipopolysaccharide, Phase variation, O-antigen, Salmonella enterica, serum resistance
Structure type: polymer chemical repeating unit
Location inside paper: table S2, subunit II
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_130701,IEDB_136105,IEDB_136906,IEDB_137472,IEDB_139421,IEDB_141794,IEDB_144983,IEDB_151528,IEDB_152206,IEDB_190606,IEDB_225177,IEDB_885823,IEDB_983930,SB_44,SB_67,SB_7,SB_72
Methods: 13C NMR, 1H NMR, methylation, NMR-2D, GC-MS, chemical analysis, mild acid hydrolysis, Western blotting, de-O-acetylation, genetic methods, SDS-Tricine-PAGE, immunization
Comments, role: de-O-acetylated S. Typhi OPS (subunit II)
Related record ID(s): 11923, 12140, 12141, 12142, 12144
NCBI Taxonomy refs (TaxIDs): 90370Reference(s) to other database(s): GTC:G27123MO, GlycomeDB:
34772
Show glycosyltransferases
NMR conditions: in D2O at 343 K
[as TSV]
13C NMR data:
Linkage Residue C1 C2 C3 C4 C5 C6
3,4,4 aXTyvp 103.6 69.9 36.2 69.4-70.4 73.2 19.3
3,4 aDManp 102.2 81.2 79.7 69.0 76.0 63.3
3 aLRhap 104.6 73.2 71.8 84.5 70.9 19.8
aDGalp 103.6 71.8 77.9 ? 74.1 62.9
1H NMR data:
Linkage Residue H1 H2 H3 H4 H5 H6
3,4,4 aXTyvp 4.88-4.91 4.04-4.05 1.81-2.05 3.61-3.63 3.75 1.26
3,4 aDManp 5.26 4.03 4.04 3.95 3.95 3.77-3.83
3 aLRhap 5.08 4.07 3.95 3.56 3.92 1.32
aDGalp 5.23 3.95 3.93 ? 4.03 3.79-3.83
1H/13C HSQC data:
Linkage Residue C1/H1 C2/H2 C3/H3 C4/H4 C5/H5 C6/H6
3,4,4 aXTyvp 103.6/4.88-4.91 69.9/4.04-4.05 36.2/1.81-2.05 69.4-70.4/3.61-3.63 73.2/3.75 19.3/1.26
3,4 aDManp 102.2/5.26 81.2/4.03 79.7/4.04 69.0/3.95 76.0/3.95 63.3/3.77-3.83
3 aLRhap 104.6/5.08 73.2/4.07 71.8/3.95 84.5/3.56 70.9/3.92 19.8/1.32
aDGalp 103.6/5.23 71.8/3.95 77.9/3.93 ?/? 74.1/4.03 62.9/3.79-3.83
1H NMR data:
| Linkage | Residue | H1 | H2 | H3 | H4 | H5 | H6 |
|---|
| 3,4,4 | aXTyvp | 4.88
4.91 | 4.04
4.05 | 1.81
2.05 | 3.61
3.63 | 3.75 | 1.26 |
| 3,4 | aDManp | 5.26 | 4.03 | 4.04 | 3.95 | 3.95 | 3.77
3.83 |
| 3 | aLRhap | 5.08 | 4.07 | 3.95 | 3.56 | 3.92 | 1.32 |
| | aDGalp | 5.23 | 3.95 | 3.93 | ? | 4.03 | 3.79
3.83 |
|
13C NMR data:
| Linkage | Residue | C1 | C2 | C3 | C4 | C5 | C6 |
|---|
| 3,4,4 | aXTyvp | 103.6 | 69.9 | 36.2 | 69.4
70.4 | 73.2 | 19.3 |
| 3,4 | aDManp | 102.2 | 81.2 | 79.7 | 69.0 | 76.0 | 63.3 |
| 3 | aLRhap | 104.6 | 73.2 | 71.8 | 84.5 | 70.9 | 19.8 |
| | aDGalp | 103.6 | 71.8 | 77.9 | ? | 74.1 | 62.9 |
|
![](nmr_drawer.py?width=750&height=130&nucleus=C&rotate_labels=false&spectrum=[{"s":103.6,"l":"1","c":[0,0,225]},{"s":69.9,"l":"2","c":[0,0,225]},{"s":36.2,"l":"3","c":[0,0,225]},{"s":69.9,"l":"4","c":[0,0,225]},{"s":73.2,"l":"5","c":[0,0,225]},{"s":19.3,"l":"6","c":[0,0,225]},{"s":102.2,"l":"1","c":[230,0,30]},{"s":81.2,"l":"2","c":[230,0,30]},{"s":79.7,"l":"3","c":[230,0,30]},{"s":69,"l":"4","c":[230,0,30]},{"s":76,"l":"5","c":[230,0,30]},{"s":63.3,"l":"6","c":[230,0,30]},{"s":104.6,"l":"1","c":[0,165,0]},{"s":73.2,"l":"2","c":[0,165,0]},{"s":71.8,"l":"3","c":[0,165,0]},{"s":84.5,"l":"4","c":[0,165,0]},{"s":70.9,"l":"5","c":[0,165,0]},{"s":19.8,"l":"6","c":[0,165,0]},{"s":103.6,"l":"1","c":[120,0,225]},{"s":71.8,"l":"2","c":[120,0,225]},{"s":77.9,"l":"3","c":[120,0,225]},{"s":74.1,"l":"5","c":[120,0,225]},{"s":62.9,"l":"6","c":[120,0,225]}])
The spectrum also has 1 signal at unknown position (not plotted). |
There is only one chemically distinct structure:
report error
Found 1 record.
Displayed record 1
