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Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation

Staphylococcus aureus causes severe, life-threatening infections that often are complicated by severe local and systemic pathologies with non-healing lesions. A classic example is S. aureus infective endocarditis (IE), where the secreted hemolysin β-toxin potentiates the disease via its sphingomyeli...

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Autores principales: Tran, Phuong M., Tang, Sharon S., Salgado-Pabón, Wilmara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851161/
https://www.ncbi.nlm.nih.gov/pubmed/35185854
http://dx.doi.org/10.3389/fmicb.2022.840236
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author Tran, Phuong M.
Tang, Sharon S.
Salgado-Pabón, Wilmara
author_facet Tran, Phuong M.
Tang, Sharon S.
Salgado-Pabón, Wilmara
author_sort Tran, Phuong M.
collection PubMed
description Staphylococcus aureus causes severe, life-threatening infections that often are complicated by severe local and systemic pathologies with non-healing lesions. A classic example is S. aureus infective endocarditis (IE), where the secreted hemolysin β-toxin potentiates the disease via its sphingomyelinase and biofilm ligase activities. Although these activities dysregulate human aortic endothelial cell activation, β-toxin effect on endothelial cell function in wound healing has not been addressed. With the use of the ex vivo rabbit aortic ring model, we provide evidence that β-toxin prevents branching microvessel formation, highlighting its ability to interfere with tissue re-vascularization and vascular repair. We show that β-toxin specifically targets both human aortic endothelial cell proliferation and cell migration and inhibits human umbilical vein endothelial cell rearrangement into capillary-like networks in vitro. Proteome arrays specific for angiogenesis-related molecules provided evidence that β-toxin promotes an inhibitory profile in endothelial cell monolayers, specifically targeting production of TIMP-1, TIMP-4, and IGFBP-3 to counter the effect of a pro-angiogenic environment. Dysregulation in the production of these molecules is known to result in sprouting defects (including deficient cell proliferation, migration, and survival), vessel instability and/or vascular regression. When endothelial cells are grown under re-endothelialization/wound healing conditions, β-toxin decreases the pro-angiogenic molecule MMP-8 and increases the anti-angiogenic molecule endostatin. Altogether, the data indicate that β-toxin is an anti-angiogenic virulence factor and highlight a mechanism where β-toxin exacerbates S. aureus invasive infections by interfering with tissue re-vascularization and vascular repair.
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spelling pubmed-88511612022-02-18 Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation Tran, Phuong M. Tang, Sharon S. Salgado-Pabón, Wilmara Front Microbiol Microbiology Staphylococcus aureus causes severe, life-threatening infections that often are complicated by severe local and systemic pathologies with non-healing lesions. A classic example is S. aureus infective endocarditis (IE), where the secreted hemolysin β-toxin potentiates the disease via its sphingomyelinase and biofilm ligase activities. Although these activities dysregulate human aortic endothelial cell activation, β-toxin effect on endothelial cell function in wound healing has not been addressed. With the use of the ex vivo rabbit aortic ring model, we provide evidence that β-toxin prevents branching microvessel formation, highlighting its ability to interfere with tissue re-vascularization and vascular repair. We show that β-toxin specifically targets both human aortic endothelial cell proliferation and cell migration and inhibits human umbilical vein endothelial cell rearrangement into capillary-like networks in vitro. Proteome arrays specific for angiogenesis-related molecules provided evidence that β-toxin promotes an inhibitory profile in endothelial cell monolayers, specifically targeting production of TIMP-1, TIMP-4, and IGFBP-3 to counter the effect of a pro-angiogenic environment. Dysregulation in the production of these molecules is known to result in sprouting defects (including deficient cell proliferation, migration, and survival), vessel instability and/or vascular regression. When endothelial cells are grown under re-endothelialization/wound healing conditions, β-toxin decreases the pro-angiogenic molecule MMP-8 and increases the anti-angiogenic molecule endostatin. Altogether, the data indicate that β-toxin is an anti-angiogenic virulence factor and highlight a mechanism where β-toxin exacerbates S. aureus invasive infections by interfering with tissue re-vascularization and vascular repair. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8851161/ /pubmed/35185854 http://dx.doi.org/10.3389/fmicb.2022.840236 Text en Copyright © 2022 Tran, Tang and Salgado-Pabón. 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 Microbiology
Tran, Phuong M.
Tang, Sharon S.
Salgado-Pabón, Wilmara
Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation
title Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation
title_full Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation
title_fullStr Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation
title_full_unstemmed Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation
title_short Staphylococcus aureus β-Toxin Exerts Anti-angiogenic Effects by Inhibiting Re-endothelialization and Neovessel Formation
title_sort staphylococcus aureus β-toxin exerts anti-angiogenic effects by inhibiting re-endothelialization and neovessel formation
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851161/
https://www.ncbi.nlm.nih.gov/pubmed/35185854
http://dx.doi.org/10.3389/fmicb.2022.840236
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