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Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis

Bartonella are Gram-negative bacterial pathogens that trigger pathological angiogenesis during infection of humans. Bartonella bacilliformis (Bb) is a neglected tropical agent endemic to South America, where it causes Carrión’s disease. Little is known about Bb’s virulence determinants or how the pa...

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Autores principales: Hicks, Linda D., Minnick, Michael F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190185/
https://www.ncbi.nlm.nih.gov/pubmed/32302357
http://dx.doi.org/10.1371/journal.pntd.0008236
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author Hicks, Linda D.
Minnick, Michael F.
author_facet Hicks, Linda D.
Minnick, Michael F.
author_sort Hicks, Linda D.
collection PubMed
description Bartonella are Gram-negative bacterial pathogens that trigger pathological angiogenesis during infection of humans. Bartonella bacilliformis (Bb) is a neglected tropical agent endemic to South America, where it causes Carrión’s disease. Little is known about Bb’s virulence determinants or how the pathogen elicits hyperproliferation of the vasculature, culminating in Peruvian warts (verruga peruana) of the skin. In this study, we determined that active infection of human umbilical vein endothelial cells (HUVECs) by live Bb induced host cell secretion of epidermal growth factor (EGF) using ELISA. Killed bacteria or lysates of various Bb strains did not cause EGF production, suggesting that an active infection was necessary for the response. Bb also caused hyperproliferation of infected HUVECs, and the mitogenic response could be inhibited by the EGF-receptor (EGFR) inhibitor, AG1478. Bb strains engineered to overexpress recombinant GroEL, evoked greater EGF production and hyperproliferation of HUVECs compared to control strains. Conditioned (spent) media from cultured HUVECs that had been previously infected by Bb were found to be mitogenic for naïve HUVECs, and the response could be inhibited by EGFR blocking with AG1478. Bb cells and cell lysates stimulated HUVEC migration and capillary-like tube formation in transmigration and Matrigel assays, respectively. To our knowledge, this is the first demonstration of EGF production by Bb-infected endothelial cells; an association that could contribute to hyperproliferation of the vascular bed during bartonellosis.
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spelling pubmed-71901852020-05-06 Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis Hicks, Linda D. Minnick, Michael F. PLoS Negl Trop Dis Research Article Bartonella are Gram-negative bacterial pathogens that trigger pathological angiogenesis during infection of humans. Bartonella bacilliformis (Bb) is a neglected tropical agent endemic to South America, where it causes Carrión’s disease. Little is known about Bb’s virulence determinants or how the pathogen elicits hyperproliferation of the vasculature, culminating in Peruvian warts (verruga peruana) of the skin. In this study, we determined that active infection of human umbilical vein endothelial cells (HUVECs) by live Bb induced host cell secretion of epidermal growth factor (EGF) using ELISA. Killed bacteria or lysates of various Bb strains did not cause EGF production, suggesting that an active infection was necessary for the response. Bb also caused hyperproliferation of infected HUVECs, and the mitogenic response could be inhibited by the EGF-receptor (EGFR) inhibitor, AG1478. Bb strains engineered to overexpress recombinant GroEL, evoked greater EGF production and hyperproliferation of HUVECs compared to control strains. Conditioned (spent) media from cultured HUVECs that had been previously infected by Bb were found to be mitogenic for naïve HUVECs, and the response could be inhibited by EGFR blocking with AG1478. Bb cells and cell lysates stimulated HUVEC migration and capillary-like tube formation in transmigration and Matrigel assays, respectively. To our knowledge, this is the first demonstration of EGF production by Bb-infected endothelial cells; an association that could contribute to hyperproliferation of the vascular bed during bartonellosis. Public Library of Science 2020-04-17 /pmc/articles/PMC7190185/ /pubmed/32302357 http://dx.doi.org/10.1371/journal.pntd.0008236 Text en © 2020 Hicks, Minnick http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hicks, Linda D.
Minnick, Michael F.
Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis
title Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis
title_full Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis
title_fullStr Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis
title_full_unstemmed Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis
title_short Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis
title_sort human vascular endothelial cells express epithelial growth factor in response to infection by bartonella bacilliformis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190185/
https://www.ncbi.nlm.nih.gov/pubmed/32302357
http://dx.doi.org/10.1371/journal.pntd.0008236
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