Salmonella Typhimurium reprograms macrophage metabolism via T3SS effector SopE2 to promote intracellular replication and virulence

Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here we show that macrophages infected with S . Typhimurium exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates. The effects on serine synthesis ar...

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Published in:Nature communications Vol. 12; no. 1; pp. 879 - 18
Main Authors: Jiang, Lingyan, Wang, Peisheng, Song, Xiaorui, Zhang, Huan, Ma, Shuangshuang, Wang, Jingting, Li, Wanwu, Lv, Runxia, Liu, Xiaoqian, Ma, Shuai, Yan, Jiaqi, Zhou, Haiyan, Huang, Di, Cheng, Zhihui, Yang, Chen, Feng, Lu, Wang, Lei
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 09.02.2021
Nature Publishing Group
Nature Portfolio
Subjects:
13/89
38/1
38/15
38/90
38/91
42/109
631/250/254
631/326/41/88
631/326/421
631/45/320
82/83
Accumulation
Animals
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Carbon sources
Disseminated infection
Gene Expression Regulation, Bacterial
Genomic Islands
Glucose - metabolism
Glyceric Acids - metabolism
Glycolysis
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - metabolism
Humanities and Social Sciences
Intermediates
Intracellular
Lactic acid
Macrophages
Macrophages - metabolism
Macrophages - microbiology
Metabolism
Mice
multidisciplinary
Pathogenicity
Pathogens
Pyruvic acid
RAW 264.7 Cells
Replication
Salmonella
Salmonella Typhimurium
Salmonella typhimurium - growth & development
Salmonella typhimurium - metabolism
Salmonella typhimurium - pathogenicity
Science
Science (multidisciplinary)
Serine
Serine - biosynthesis
Signal Transduction
Synthesis
Type III Secretion Systems - genetics
Type III Secretion Systems - metabolism
Virulence
Virulence factors
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here we show that macrophages infected with S . Typhimurium exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates. The effects on serine synthesis are mediated by bacterial protein SopE2, a type III secretion system (T3SS) effector encoded in pathogenicity island SPI-1. The changes in host metabolism promote intracellular replication of S . Typhimurium via two mechanisms: decreased glucose levels lead to upregulated bacterial uptake of 2- and 3-phosphoglycerate and phosphoenolpyruvate (carbon sources), while increased pyruvate and lactate levels induce upregulation of another pathogenicity island, SPI-2, known to encode virulence factors. Pharmacological or genetic inhibition of host glycolysis, activation of host serine synthesis, or deletion of either the bacterial transport or signal sensor systems for those host glycolytic intermediates impairs S . Typhimurium replication or virulence. Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here, Jiang et al. show that infected macrophages exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates that promote intracellular replication and virulence of S . Typhimurium.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-21186-4