Cargando…
Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins
Bacterial AB-type toxins are proteins released by the producing bacteria and are the causative agents for several severe diseases including cholera, whooping cough, diphtheria or enteric diseases. Their unique AB-type structure enables their uptake into mammalian cells via sophisticated mechanisms e...
Autor principal: | |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387773/ https://www.ncbi.nlm.nih.gov/pubmed/35992160 http://dx.doi.org/10.3389/fcimb.2022.938015 |
_version_ | 1784770074923499520 |
---|---|
author | Ernst, Katharina |
author_facet | Ernst, Katharina |
author_sort | Ernst, Katharina |
collection | PubMed |
description | Bacterial AB-type toxins are proteins released by the producing bacteria and are the causative agents for several severe diseases including cholera, whooping cough, diphtheria or enteric diseases. Their unique AB-type structure enables their uptake into mammalian cells via sophisticated mechanisms exploiting cellular uptake and transport pathways. The binding/translocation B-subunit facilitates binding of the toxin to a specific receptor on the cell surface. This is followed by receptor-mediated endocytosis. Then the enzymatically active A-subunit either escapes from endosomes in a pH-dependent manner or the toxin is further transported through the Golgi to the endoplasmic reticulum from where the A-subunit translocates into the cytosol. In the cytosol, the A-subunits enzymatically modify a specific substrate which leads to cellular reactions resulting in clinical symptoms that can be life-threatening. Both intracellular uptake routes require the A-subunit to unfold to either fit through a pore formed by the B-subunit into the endosomal membrane or to be recognized by the ER-associated degradation pathway. This led to the hypothesis that folding helper enzymes such as chaperones and peptidyl-prolyl cis/trans isomerases are required to assist the translocation of the A-subunit into the cytosol and/or facilitate their refolding into an enzymatically active conformation. This review article gives an overview about the role of heat shock proteins Hsp90 and Hsp70 as well as of peptidyl-prolyl cis/trans isomerases of the cyclophilin and FK506 binding protein families during uptake of bacterial AB-type toxins with a focus on clostridial binary toxins Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin, Clostridioides difficile CDT toxin, as well as diphtheria toxin, pertussis toxin and cholera toxin. |
format | Online Article Text |
id | pubmed-9387773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93877732022-08-19 Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins Ernst, Katharina Front Cell Infect Microbiol Cellular and Infection Microbiology Bacterial AB-type toxins are proteins released by the producing bacteria and are the causative agents for several severe diseases including cholera, whooping cough, diphtheria or enteric diseases. Their unique AB-type structure enables their uptake into mammalian cells via sophisticated mechanisms exploiting cellular uptake and transport pathways. The binding/translocation B-subunit facilitates binding of the toxin to a specific receptor on the cell surface. This is followed by receptor-mediated endocytosis. Then the enzymatically active A-subunit either escapes from endosomes in a pH-dependent manner or the toxin is further transported through the Golgi to the endoplasmic reticulum from where the A-subunit translocates into the cytosol. In the cytosol, the A-subunits enzymatically modify a specific substrate which leads to cellular reactions resulting in clinical symptoms that can be life-threatening. Both intracellular uptake routes require the A-subunit to unfold to either fit through a pore formed by the B-subunit into the endosomal membrane or to be recognized by the ER-associated degradation pathway. This led to the hypothesis that folding helper enzymes such as chaperones and peptidyl-prolyl cis/trans isomerases are required to assist the translocation of the A-subunit into the cytosol and/or facilitate their refolding into an enzymatically active conformation. This review article gives an overview about the role of heat shock proteins Hsp90 and Hsp70 as well as of peptidyl-prolyl cis/trans isomerases of the cyclophilin and FK506 binding protein families during uptake of bacterial AB-type toxins with a focus on clostridial binary toxins Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin, Clostridioides difficile CDT toxin, as well as diphtheria toxin, pertussis toxin and cholera toxin. Frontiers Media S.A. 2022-08-04 /pmc/articles/PMC9387773/ /pubmed/35992160 http://dx.doi.org/10.3389/fcimb.2022.938015 Text en Copyright © 2022 Ernst https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Ernst, Katharina Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins |
title | Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins |
title_full | Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins |
title_fullStr | Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins |
title_full_unstemmed | Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins |
title_short | Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins |
title_sort | requirement of peptidyl-prolyl cis/trans isomerases and chaperones for cellular uptake of bacterial ab-type toxins |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387773/ https://www.ncbi.nlm.nih.gov/pubmed/35992160 http://dx.doi.org/10.3389/fcimb.2022.938015 |
work_keys_str_mv | AT ernstkatharina requirementofpeptidylprolylcistransisomerasesandchaperonesforcellularuptakeofbacterialabtypetoxins |