Glycan encapsulated gold nanoparticles selectively inhibit shiga toxins 1 and 2.
Glycan encapsulated gold nanoparticles selectively inhibit shiga toxins 1 and 2.
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DOI:
10.1021/bc100095w
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发表时间:
2010-08-18
影响因子:
4.7
通讯作者:
Iyer, Suri S.
中科院分区:
文献类型:
--
作者:
Kulkarni, Ashish A.;Fuller, Cynthia;Korman, Henry;Weiss, Alison A.;Iyer, Suri S.
Shiga toxins (Stx) released by Escherichia coli O157:H7 and Shigella dysentriae, cause life-threatening conditions that include hemolytic-uremic syndrome (HUS), kidney failure and neurological complications. Cellular entry is mediated by the B subunit of the AB5 toxin, which recognizes cell surface glycolipids present in lipid raft like structures. We developed gold glyconanoparticles that present a multivalent display similar to the cell surface glycolipids to compete for these toxins. These highly soluble glyconanoparticles were nontoxic to the Vero monkey kidney cell line and protected Vero cells from Stx-mediated toxicity in a dose dependent manner. The inhibition is highly dependent on the structure and density of the glycans; selective inhibition of Stx1 and the more clinically relevant Stx2 was achieved. Interestingly, natural variants of Stx2, Stx2c and Stx2d, possessing minimal amino acid variation in the receptor binding site of the B subunit or changes in the A subunit were not neutralized by either the Stx1- or Stx2-specific gold glyconanoparticles. Our results suggest that tailored glyconanoparticles that mimic the natural display of glycans in lipid rafts could serve as potential therapeutics for Stx1 and Stx2. However, a few amino acid changes in emerging Stx2 variants can change receptor specificity, and further research is needed to develop receptor mimics for the emerging variants of Stx2.
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影响因子:
4.9
作者:
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通讯作者:
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影响因子:
9.4
作者:
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影响因子:
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作者:
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Iyer, Suri S.
影响因子:
64.8
作者:
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通讯作者:
Bundle, DR
DOI:
10.1039/c39950001655
发表时间:
1995-08-21
影响因子:
--
作者:
BRUST, M;FINK, J;KIELY, C
通讯作者:
KIELY, C