| Title |
Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin
|
|---|---|
| Published in |
Nature, December 2008
|
| DOI | 10.1038/nature07428 |
| Pubmed ID | |
| Authors |
Emma Byres, Adrienne W. Paton, James C. Paton, Jonas C. Löfling, David F. Smith, Matthew C. J. Wilce, Ursula M. Talbot, Damien C. Chong, Hai Yu, Shengshu Huang, Xi Chen, Nissi M. Varki, Ajit Varki, Jamie Rossjohn, Travis Beddoe |
| Abstract |
AB(5) toxins comprise an A subunit that corrupts essential eukaryotic cell functions, and pentameric B subunits that direct target-cell uptake after binding surface glycans. Subtilase cytotoxin (SubAB) is an AB(5) toxin secreted by Shiga toxigenic Escherichia coli (STEC), which causes serious gastrointestinal disease in humans. SubAB causes haemolytic uraemic syndrome-like pathology in mice through SubA-mediated cleavage of BiP/GRP78, an essential endoplasmic reticulum chaperone. Here we show that SubB has a strong preference for glycans terminating in the sialic acid N-glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesized in humans. Structures of SubB-Neu5Gc complexes revealed the basis for this specificity, and mutagenesis of key SubB residues abrogated in vitro glycan recognition, cell binding and cytotoxicity. SubAB specificity for Neu5Gc was confirmed using mouse tissues with a human-like deficiency of Neu5Gc and human cell lines fed with Neu5Gc. Despite lack of Neu5Gc biosynthesis in humans, assimilation of dietary Neu5Gc creates high-affinity receptors on human gut epithelia and kidney vasculature. This, and the lack of Neu5Gc-containing body fluid competitors in humans, confers susceptibility to the gastrointestinal and systemic toxicities of SubAB. Ironically, foods rich in Neu5Gc are the most common source of STEC contamination. Thus a bacterial toxin's receptor is generated by metabolic incorporation of an exogenous factor derived from food. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 17% |
| United Kingdom | 1 | 17% |
| Unknown | 4 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
| Scientists | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 181 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 2% |
| Canada | 3 | 2% |
| Germany | 2 | 1% |
| India | 1 | <1% |
| United Kingdom | 1 | <1% |
| Japan | 1 | <1% |
| Spain | 1 | <1% |
| Unknown | 169 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 42 | 23% |
| Researcher | 42 | 23% |
| Professor > Associate Professor | 16 | 9% |
| Student > Bachelor | 15 | 8% |
| Professor | 14 | 8% |
| Other | 32 | 18% |
| Unknown | 20 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 74 | 41% |
| Biochemistry, Genetics and Molecular Biology | 24 | 13% |
| Chemistry | 18 | 10% |
| Immunology and Microbiology | 16 | 9% |
| Medicine and Dentistry | 9 | 5% |
| Other | 11 | 6% |
| Unknown | 29 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 27. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 December 2022.
All research outputs
#1,419,998
of 25,483,400 outputs
Outputs from Nature
#37,378
of 98,074 outputs
Outputs of similar age
#5,300
of 179,980 outputs
Outputs of similar age from Nature
#83
of 517 outputs
Altmetric has tracked 25,483,400 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 98,074 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.5. This one has gotten more attention than average, scoring higher than 61% of its peers.
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