In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 8 ( 2023-8-18), p. e3002198-
Abstract:
Pathogenic bacteria proliferating inside mammalian host cells need to rapidly adapt to the intracellular environment. How they achieve this and scavenge essential nutrients from the host has been an open question due to the difficulties in distinguishing between bacterial and host metabolites in situ. Here, we capitalized on the inability of mammalian cells to metabolize mannitol to develop a stable isotopic labeling approach to track Salmonella enterica metabolites during intracellular proliferation in host macrophage and epithelial cells. By measuring label incorporation into Salmonella metabolites with liquid chromatography–mass spectrometry (LC–MS), and combining it with metabolic modeling, we identify relevant carbon sources used by Salmonella , uncover routes of their metabolization, and quantify relative reaction rates in central carbon metabolism. Our results underline the importance of the Entner–Doudoroff pathway (EDP) and the phosphoenolpyruvate carboxylase for intracellularly proliferating Salmonella . More broadly, our metabolic labeling strategy opens novel avenues for understanding the metabolism of pathogens inside host cells.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002198
DOI:
10.1371/journal.pbio.3002198.g001
DOI:
10.1371/journal.pbio.3002198.g002
DOI:
10.1371/journal.pbio.3002198.g003
DOI:
10.1371/journal.pbio.3002198.g004
DOI:
10.1371/journal.pbio.3002198.g005
DOI:
10.1371/journal.pbio.3002198.g006
DOI:
10.1371/journal.pbio.3002198.s001
DOI:
10.1371/journal.pbio.3002198.s002
DOI:
10.1371/journal.pbio.3002198.s003
DOI:
10.1371/journal.pbio.3002198.s004
DOI:
10.1371/journal.pbio.3002198.s005
DOI:
10.1371/journal.pbio.3002198.s006
DOI:
10.1371/journal.pbio.3002198.s007
DOI:
10.1371/journal.pbio.3002198.s008
DOI:
10.1371/journal.pbio.3002198.s009
DOI:
10.1371/journal.pbio.3002198.s010
DOI:
10.1371/journal.pbio.3002198.s011
DOI:
10.1371/journal.pbio.3002198.s012
DOI:
10.1371/journal.pbio.3002198.s013
DOI:
10.1371/journal.pbio.3002198.s014
DOI:
10.1371/journal.pbio.3002198.s015
DOI:
10.1371/journal.pbio.3002198.s016
DOI:
10.1371/journal.pbio.3002198.s017
DOI:
10.1371/journal.pbio.3002198.s018
DOI:
10.1371/journal.pbio.3002198.s019
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X