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Salmonella enterica Serovar Typhi Induces Host Metabolic Reprogramming to Increase Glucose Availability for Intracellular Replication

by 1,2, 1,2, 1,2, 1,2, 1,2, 1,2,* and 1,2,*
1
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China
2
Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Rustam I. Aminov
Int. J. Mol. Sci. 2021, 22(18), 10003; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810003
Received: 18 August 2021 / Revised: 13 September 2021 / Accepted: 14 September 2021 / Published: 16 September 2021
(This article belongs to the Section Molecular Microbiology)
Salmonella enterica serovar Typhi (S. Typhi) is a human-limited intracellular pathogen and the cause of typhoid fever, a severe systemic disease. Pathogen–host interaction at the metabolic level affects the pathogenicity of intracellular pathogens, but it remains unclear how S. Typhi infection influences host metabolism for its own benefit. Herein, using metabolomics and transcriptomics analyses, combined with in vitro and in vivo infection assays, we investigated metabolic responses in human macrophages during S. Typhi infection, and the impact of these responses on S. Typhi intracellular replication and systemic pathogenicity. We observed increased glucose content, higher rates of glucose uptake and glycolysis, and decreased oxidative phosphorylation in S. Typhi-infected human primary macrophages. Replication in human macrophages and the bacterial burden in systemic organs of humanized mice were reduced by either the inhibition of host glucose uptake or a mutation of the bacterial glucose uptake system, indicating that S. Typhi utilizes host-derived glucose to enhance intracellular replication and virulence. Thus, S. Typhi promotes its pathogenicity by inducing metabolic changes in host macrophages and utilizing the glucose that subsequently accumulates as a nutrient for intracellular replication. Our findings provide the first metabolic signature of S. Typhi-infected host cells and identifies a new strategy utilized by S. Typhi for intracellular replication. View Full-Text
Keywords: S. Typhi; glycolysis; glucose utilization; intracellular replication; pathogenesis S. Typhi; glycolysis; glucose utilization; intracellular replication; pathogenesis
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MDPI and ACS Style

Wang, J.; Ma, S.; Li, W.; Wang, X.; Huang, D.; Jiang, L.; Feng, L. Salmonella enterica Serovar Typhi Induces Host Metabolic Reprogramming to Increase Glucose Availability for Intracellular Replication. Int. J. Mol. Sci. 2021, 22, 10003. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810003

AMA Style

Wang J, Ma S, Li W, Wang X, Huang D, Jiang L, Feng L. Salmonella enterica Serovar Typhi Induces Host Metabolic Reprogramming to Increase Glucose Availability for Intracellular Replication. International Journal of Molecular Sciences. 2021; 22(18):10003. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810003

Chicago/Turabian Style

Wang, Jingting, Shuai Ma, Wanwu Li, Xinyue Wang, Di Huang, Lingyan Jiang, and Lu Feng. 2021. "Salmonella enterica Serovar Typhi Induces Host Metabolic Reprogramming to Increase Glucose Availability for Intracellular Replication" International Journal of Molecular Sciences 22, no. 18: 10003. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810003

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