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Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy
Shiga toxin (STx) produced by Shigella and closely related Shiga toxin 1 and 2 (STx1 and STx2) synthesized by Shiga toxin-producing Escherichia coli (STEC) are bacterial AB(5) toxins. All three toxins target kidney cells and may cause life-threatening renal disease. While Shigella infections can be...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290323/ https://www.ncbi.nlm.nih.gov/pubmed/32456007 http://dx.doi.org/10.3390/toxins12050342 |
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author | Li, Danyang Selyunin, Andrey Mukhopadhyay, Somshuvra |
author_facet | Li, Danyang Selyunin, Andrey Mukhopadhyay, Somshuvra |
author_sort | Li, Danyang |
collection | PubMed |
description | Shiga toxin (STx) produced by Shigella and closely related Shiga toxin 1 and 2 (STx1 and STx2) synthesized by Shiga toxin-producing Escherichia coli (STEC) are bacterial AB(5) toxins. All three toxins target kidney cells and may cause life-threatening renal disease. While Shigella infections can be treated with antibiotics, resistance is increasing. Moreover, antibiotic therapy is contraindicated for STEC, and there are no definitive treatments for STEC-induced disease. To exert cellular toxicity, STx, STx1, and STx2 must undergo retrograde trafficking to reach their cytosolic target, ribosomes. Direct transport from early endosomes to the Golgi apparatus is an essential step that allows the toxins to bypass degradative late endosomes and lysosomes. The essentiality of this transport step also makes it an ideal target for the development of small-molecule inhibitors of toxin trafficking as potential therapeutics. Here, we review the recent advances in understanding the molecular mechanisms of the early endosome-to-Golgi transport of STx, STx1, and STx2, as well as the development of small-molecule inhibitors of toxin trafficking that act at the endosome/Golgi interface. |
format | Online Article Text |
id | pubmed-7290323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72903232020-06-15 Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy Li, Danyang Selyunin, Andrey Mukhopadhyay, Somshuvra Toxins (Basel) Review Shiga toxin (STx) produced by Shigella and closely related Shiga toxin 1 and 2 (STx1 and STx2) synthesized by Shiga toxin-producing Escherichia coli (STEC) are bacterial AB(5) toxins. All three toxins target kidney cells and may cause life-threatening renal disease. While Shigella infections can be treated with antibiotics, resistance is increasing. Moreover, antibiotic therapy is contraindicated for STEC, and there are no definitive treatments for STEC-induced disease. To exert cellular toxicity, STx, STx1, and STx2 must undergo retrograde trafficking to reach their cytosolic target, ribosomes. Direct transport from early endosomes to the Golgi apparatus is an essential step that allows the toxins to bypass degradative late endosomes and lysosomes. The essentiality of this transport step also makes it an ideal target for the development of small-molecule inhibitors of toxin trafficking as potential therapeutics. Here, we review the recent advances in understanding the molecular mechanisms of the early endosome-to-Golgi transport of STx, STx1, and STx2, as well as the development of small-molecule inhibitors of toxin trafficking that act at the endosome/Golgi interface. MDPI 2020-05-22 /pmc/articles/PMC7290323/ /pubmed/32456007 http://dx.doi.org/10.3390/toxins12050342 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Li, Danyang Selyunin, Andrey Mukhopadhyay, Somshuvra Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy |
title | Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy |
title_full | Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy |
title_fullStr | Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy |
title_full_unstemmed | Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy |
title_short | Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy |
title_sort | targeting the early endosome-to-golgi transport of shiga toxins as a therapeutic strategy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290323/ https://www.ncbi.nlm.nih.gov/pubmed/32456007 http://dx.doi.org/10.3390/toxins12050342 |
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