Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry

In this study, we measured the levels of elements in human brain microvascular endothelial cells (ECs) infected with T. gondii. ECs were infected with tachyzoites of the RH strain, and at 6, 24, and 48 hours post infection (hpi), the intracellular concentrations of elements were determined using a s...

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Main Authors: Al-sandaqchi, Alaa T., Brignell, Chris, Collingwood, Joanna F., Geraki, Kalotina, Mirkes, Evgeny M., Kong, Kenny, Castellanos, Marcos, May, Sean T., Stevenson, Carl W., Elsheikha, Hany M.
Format: Article
Language:English
Published: Royal Society of Chemistry 2018
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Online Access:https://eprints.nottingham.ac.uk/55172/
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author Al-sandaqchi, Alaa T.
Brignell, Chris
Collingwood, Joanna F.
Geraki, Kalotina
Mirkes, Evgeny M.
Kong, Kenny
Castellanos, Marcos
May, Sean T.
Stevenson, Carl W.
Elsheikha, Hany M.
author_facet Al-sandaqchi, Alaa T.
Brignell, Chris
Collingwood, Joanna F.
Geraki, Kalotina
Mirkes, Evgeny M.
Kong, Kenny
Castellanos, Marcos
May, Sean T.
Stevenson, Carl W.
Elsheikha, Hany M.
author_sort Al-sandaqchi, Alaa T.
building Nottingham Research Data Repository
collection Online Access
description In this study, we measured the levels of elements in human brain microvascular endothelial cells (ECs) infected with T. gondii. ECs were infected with tachyzoites of the RH strain, and at 6, 24, and 48 hours post infection (hpi), the intracellular concentrations of elements were determined using a synchrotron–microfocus X-ray fluorescence microscopy (μ-XRF) system. This method enabled the quantification of the concentrations of Zn and Ca in infected and uninfected (control) ECs at sub-micron spatial resolution. T. gondii-hosting ECs contained less Zn than uninfected cells only at 48 hpi (p < 0.01). The level of Ca was not significantly different between infected and control cells (p > 0.05). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis revealed infection-specific metallome profiles characterized by significant increases in the intracellular levels of Zn, Fe, Mn and Cu at 48 hpi (p < 0.01), and significant reductions in the extracellular concentrations of Co, Cu, Mo, V, and Ag at 24 hpi (p < 0.05) compared with control cells. Zn constituted the largest part (74%) of the total metal composition (metallome) of the parasite. Gene expression analysis showed infection-specific upregulation in the expression of five genes, MT1JP, MT1M, MT1E, MT1F, and MT1X, belonging to the metallothionein gene family. These results point to a possible correlation between T. gondii infection and increased expression of MT1 isoforms and altered intracellular levels of elements, especially Zn and Fe. Taken together, a combined μ-XRF and ICP-MS approach is promising for studies of the role of elements in mediating host–parasite interaction.
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spelling nottingham-551722019-09-05T04:30:53Z https://eprints.nottingham.ac.uk/55172/ Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry Al-sandaqchi, Alaa T. Brignell, Chris Collingwood, Joanna F. Geraki, Kalotina Mirkes, Evgeny M. Kong, Kenny Castellanos, Marcos May, Sean T. Stevenson, Carl W. Elsheikha, Hany M. In this study, we measured the levels of elements in human brain microvascular endothelial cells (ECs) infected with T. gondii. ECs were infected with tachyzoites of the RH strain, and at 6, 24, and 48 hours post infection (hpi), the intracellular concentrations of elements were determined using a synchrotron–microfocus X-ray fluorescence microscopy (μ-XRF) system. This method enabled the quantification of the concentrations of Zn and Ca in infected and uninfected (control) ECs at sub-micron spatial resolution. T. gondii-hosting ECs contained less Zn than uninfected cells only at 48 hpi (p < 0.01). The level of Ca was not significantly different between infected and control cells (p > 0.05). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis revealed infection-specific metallome profiles characterized by significant increases in the intracellular levels of Zn, Fe, Mn and Cu at 48 hpi (p < 0.01), and significant reductions in the extracellular concentrations of Co, Cu, Mo, V, and Ag at 24 hpi (p < 0.05) compared with control cells. Zn constituted the largest part (74%) of the total metal composition (metallome) of the parasite. Gene expression analysis showed infection-specific upregulation in the expression of five genes, MT1JP, MT1M, MT1E, MT1F, and MT1X, belonging to the metallothionein gene family. These results point to a possible correlation between T. gondii infection and increased expression of MT1 isoforms and altered intracellular levels of elements, especially Zn and Fe. Taken together, a combined μ-XRF and ICP-MS approach is promising for studies of the role of elements in mediating host–parasite interaction. Royal Society of Chemistry 2018-09-05 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/55172/1/Author%20accepted%20manuscript_Alsandaqchi%20et%20al-Metallomics.pdf Al-sandaqchi, Alaa T., Brignell, Chris, Collingwood, Joanna F., Geraki, Kalotina, Mirkes, Evgeny M., Kong, Kenny, Castellanos, Marcos, May, Sean T., Stevenson, Carl W. and Elsheikha, Hany M. (2018) Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry. Metallomics . ISSN 1756-591X Toxoplasma gondii blood-brain barrier host-pathogen interaction label-free imaging X-ray fluorescence spectromicroscopy; Mass Spectrometry http://pubs.rsc.org/en/Content/ArticleLanding/2018/MT/C8MT00136G#!divAbstract doi:10.1039/C8MT00136G doi:10.1039/C8MT00136G
spellingShingle Toxoplasma gondii
blood-brain barrier
host-pathogen interaction
label-free imaging
X-ray fluorescence spectromicroscopy; Mass Spectrometry
Al-sandaqchi, Alaa T.
Brignell, Chris
Collingwood, Joanna F.
Geraki, Kalotina
Mirkes, Evgeny M.
Kong, Kenny
Castellanos, Marcos
May, Sean T.
Stevenson, Carl W.
Elsheikha, Hany M.
Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry
title Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry
title_full Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry
title_fullStr Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry
title_full_unstemmed Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry
title_short Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry
title_sort metallome of cerebrovascular endothelial cells infected with toxoplasma gondii using μ-xrf imaging and inductively coupled plasma mass spectrometry
topic Toxoplasma gondii
blood-brain barrier
host-pathogen interaction
label-free imaging
X-ray fluorescence spectromicroscopy; Mass Spectrometry
url https://eprints.nottingham.ac.uk/55172/
https://eprints.nottingham.ac.uk/55172/
https://eprints.nottingham.ac.uk/55172/