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Holistic characterization of a salmonella typhimurium infection model using integrated molecular imaging.

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Title: Holistic characterization of a salmonella typhimurium infection model using integrated molecular imaging.
Authors: Strittmatter, N
Kanvatirth, P
Inglese, P
Race, AM
Nilsson, A
Dannhorn, A
Kudo, H
Goldin, RD
Ling, S
Wong, E
Seeliger, F
Serra, MP
Hoffmann, S
Maglennon, G
Hamm, G
Atkinson, J
Jones, S
Bunch, J
Andrén, PE
Takats, Z
Goodwin, RJA
Mastroeni, P
Item Type: Journal Article
Abstract: A more complete and holistic view on host-microbe interactions is needed to understand the physiological and cellular barriers that affect the efficacy of drug treatments and allow the discovery and development of new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry imaging (MSI) and same section imaging mass cytometry (IMC) to study the effects of Salmonella Typhimurium infection in the liver of a mouse model using the S. Typhimurium strains SL3261 and SL1344. This approach enables correlation of tissue morphology and specific cell phenotypes with molecular images of tissue metabolism. IMC revealed a marked increase in immune cell markers and localization in immune aggregates in infected tissues. A correlative computational method (network analysis) was deployed to find metabolic features associated with infection and revealed metabolic clusters of acetyl carnitines, as well as phosphatidylcholine and phosphatidylethanolamine plasmalogen species, which could be associated with pro-inflammatory immune cell types. By developing an IMC marker for the detection of Salmonella LPS, we were further able to identify and characterize those cell types which contained S. Typhimurium.
Issue Date: 1-Dec-2021
Date of Acceptance: 15-Oct-2021
URI: http://hdl.handle.net/10044/1/93662
DOI: 10.1021/jasms.1c00240
ISSN: 1044-0305
Publisher: American Chemical Society
Start Page: 2791
End Page: 2802
Journal / Book Title: Journal of the American Society for Mass Spectrometry
Volume: 32
Issue: 12
Copyright Statement: t © 2021 American Society for Mass Spectrometry. Published by American Chemical Society. All rights reserved. RIGHTS & PERMISSIONS
Keywords: Salmonella infection
imaging mass cytometry
mass spectrometry imaging
multimodal data integration
network analysis
Salmonella infection
imaging mass cytometry
mass spectrometry imaging
multimodal data integration
network analysis
Analytical Chemistry
0301 Analytical Chemistry
0304 Medicinal and Biomolecular Chemistry
0306 Physical Chemistry (incl. Structural)
Publication Status: Published
Conference Place: United States
Embargo Date: Embargoed for 12 months after publication date
Appears in Collections:Department of Metabolism, Digestion and Reproduction