Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier

Staphylococcus aureus is a leading cause of infections world-wide. Once this pathogen has reached the bloodstream, it can invade different parts of the human body by crossing the endothelial barrier. Infected endothelial cells may be lysed by bacterial products, but the bacteria may also persist int...

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Autores principales:	Elisa J.M. Raineri, Harita Yedavally, Anna Salvati, Jan Maarten van Dijl
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	staphylococcus aureus mrsa endothelium invasion intracellular Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/f5d8cf3d4c144c2a9e0bacb174c6d1ca
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spelling	oai:doaj.org-article:f5d8cf3d4c144c2a9e0bacb174c6d1ca2021-11-17T14:21:59ZTime-resolved analysis of Staphylococcus aureus invading the endothelial barrier2150-55942150-560810.1080/21505594.2020.1844418https://doaj.org/article/f5d8cf3d4c144c2a9e0bacb174c6d1ca2020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1844418https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Staphylococcus aureus is a leading cause of infections world-wide. Once this pathogen has reached the bloodstream, it can invade different parts of the human body by crossing the endothelial barrier. Infected endothelial cells may be lysed by bacterial products, but the bacteria may also persist intracellularly, where they are difficult to eradicate with antibiotics and cause relapses of infection. Our present study was aimed at investigating the fate of methicillin resistant S. aureus (MRSA) isolates of the USA300 lineage with different epidemiological origin inside endothelial cells. To this end, we established two in vitro infection models based on primary human umbilical vein endothelial cells (HUVEC), which mimic conditions of the endothelium when infection occurs. For comparison, the laboratory strain S. aureus HG001 was used. As shown by flow cytometry and fluorescence- or electron microscopy, differentiation of HUVEC into a cell barrier with cell-cell junctions sets limits to the rates of bacterial internalization, the numbers of internalized bacteria, the percentage of infected cells, and long-term intracellular bacterial survival. Clear strain-specific differences were observed with the HG001 strain infecting the highest numbers of HUVEC and displaying the longest intracellular persistence, whereas the MRSA strains reproduced faster intracellularly. Nonetheless, all internalized bacteria remained confined in membrane-enclosed LAMP-1-positive lysosomal or vacuolar compartments. Once internalized, the bacteria had a higher propensity to persist within the differentiated endothelial cell barrier, probably because internalization of lower numbers of bacteria was less toxic. Altogether, our findings imply that intact endothelial barriers are more likely to sustain persistent intracellular infection.Elisa J.M. RaineriHarita YedavallyAnna SalvatiJan Maarten van DijlTaylor & Francis Grouparticlestaphylococcus aureusmrsaendotheliuminvasionintracellularInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1623-1639 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	staphylococcus aureus mrsa endothelium invasion intracellular Infectious and parasitic diseases RC109-216
spellingShingle	staphylococcus aureus mrsa endothelium invasion intracellular Infectious and parasitic diseases RC109-216 Elisa J.M. Raineri Harita Yedavally Anna Salvati Jan Maarten van Dijl Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier
description	Staphylococcus aureus is a leading cause of infections world-wide. Once this pathogen has reached the bloodstream, it can invade different parts of the human body by crossing the endothelial barrier. Infected endothelial cells may be lysed by bacterial products, but the bacteria may also persist intracellularly, where they are difficult to eradicate with antibiotics and cause relapses of infection. Our present study was aimed at investigating the fate of methicillin resistant S. aureus (MRSA) isolates of the USA300 lineage with different epidemiological origin inside endothelial cells. To this end, we established two in vitro infection models based on primary human umbilical vein endothelial cells (HUVEC), which mimic conditions of the endothelium when infection occurs. For comparison, the laboratory strain S. aureus HG001 was used. As shown by flow cytometry and fluorescence- or electron microscopy, differentiation of HUVEC into a cell barrier with cell-cell junctions sets limits to the rates of bacterial internalization, the numbers of internalized bacteria, the percentage of infected cells, and long-term intracellular bacterial survival. Clear strain-specific differences were observed with the HG001 strain infecting the highest numbers of HUVEC and displaying the longest intracellular persistence, whereas the MRSA strains reproduced faster intracellularly. Nonetheless, all internalized bacteria remained confined in membrane-enclosed LAMP-1-positive lysosomal or vacuolar compartments. Once internalized, the bacteria had a higher propensity to persist within the differentiated endothelial cell barrier, probably because internalization of lower numbers of bacteria was less toxic. Altogether, our findings imply that intact endothelial barriers are more likely to sustain persistent intracellular infection.
format	article
author	Elisa J.M. Raineri Harita Yedavally Anna Salvati Jan Maarten van Dijl
author_facet	Elisa J.M. Raineri Harita Yedavally Anna Salvati Jan Maarten van Dijl
author_sort	Elisa J.M. Raineri
title	Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier
title_short	Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier
title_full	Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier
title_fullStr	Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier
title_full_unstemmed	Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier
title_sort	time-resolved analysis of staphylococcus aureus invading the endothelial barrier
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/f5d8cf3d4c144c2a9e0bacb174c6d1ca
work_keys_str_mv	AT elisajmraineri timeresolvedanalysisofstaphylococcusaureusinvadingtheendothelialbarrier AT haritayedavally timeresolvedanalysisofstaphylococcusaureusinvadingtheendothelialbarrier AT annasalvati timeresolvedanalysisofstaphylococcusaureusinvadingtheendothelialbarrier AT janmaartenvandijl timeresolvedanalysisofstaphylococcusaureusinvadingtheendothelialbarrier
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Time-resolved analysis of Staphylococcus aureus invading the endothelial barrier

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