Cargando…
Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors
BACKGROUND: It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2006
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386683/ https://www.ncbi.nlm.nih.gov/pubmed/16464252 http://dx.doi.org/10.1186/1471-2180-6-8 |
_version_ | 1782126875649245184 |
---|---|
author | Popova, Taissia G Millis, Bryan Bradburne, Chris Nazarenko, Svetlana Bailey, Charles Chandhoke, Vikas Popov, Serguei G |
author_facet | Popova, Taissia G Millis, Bryan Bradburne, Chris Nazarenko, Svetlana Bailey, Charles Chandhoke, Vikas Popov, Serguei G |
author_sort | Popova, Taissia G |
collection | PubMed |
description | BACKGROUND: It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. RESULTS: The isolated anthrax hemolytic proteins AnlB (sphingomyelinase) and AnlO (cholesterol-binding pore-forming factor), as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C) cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT) also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne) spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. CONCLUSION: The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection. |
format | Text |
id | pubmed-1386683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-13866832006-03-02 Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors Popova, Taissia G Millis, Bryan Bradburne, Chris Nazarenko, Svetlana Bailey, Charles Chandhoke, Vikas Popov, Serguei G BMC Microbiol Research Article BACKGROUND: It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. RESULTS: The isolated anthrax hemolytic proteins AnlB (sphingomyelinase) and AnlO (cholesterol-binding pore-forming factor), as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C) cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT) also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne) spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. CONCLUSION: The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection. BioMed Central 2006-02-07 /pmc/articles/PMC1386683/ /pubmed/16464252 http://dx.doi.org/10.1186/1471-2180-6-8 Text en Copyright © 2006 Popova et al; licensee BioMed Central Ltd. |
spellingShingle | Research Article Popova, Taissia G Millis, Bryan Bradburne, Chris Nazarenko, Svetlana Bailey, Charles Chandhoke, Vikas Popov, Serguei G Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
title | Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
title_full | Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
title_fullStr | Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
title_full_unstemmed | Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
title_short | Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
title_sort | acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386683/ https://www.ncbi.nlm.nih.gov/pubmed/16464252 http://dx.doi.org/10.1186/1471-2180-6-8 |
work_keys_str_mv | AT popovataissiag accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors AT millisbryan accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors AT bradburnechris accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors AT nazarenkosvetlana accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors AT baileycharles accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors AT chandhokevikas accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors AT popovsergueig accelerationofepithelialcellsyndecan1sheddingbyanthraxhemolyticvirulencefactors |