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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Vydáno v:	Nature communications Ročník 12; číslo 1; s. 879 - 18
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 09.02.2021 Nature Publishing Group Nature Portfolio
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-21186-4