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Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells
Published on: August 5, 2016
Metabolomic Analysis of Murine Tissues Infected with Brucella melitensis
Bárbara Ponzilacqua-Silva1,2, Alexis S Dadelahi1,2, Charles R Moley1,2
1Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri.
Abstract:
Brucella is a gram negative, facultative, intracellular bacterial pathogen that constitutes a substantial threat to human and animal health. Brucella can replicate in a variety of tissues and can induce immune responses that alter host metabolite availability. Here, mice were infected with B. melitensis and murine spleens, livers, and female reproductive tracts were analyzed by GC-MS to determine tissue-specific metabolic changes at one-, two- and four- weeks post infection. The most remarkable changes were observed at two-weeks post-infection when relative to uninfected tissues, 42 of 329 detected metabolites in reproductive tracts were significantly altered by Brucella infection, while in spleens and livers, 68/205 and 139/330 metabolites were significantly changed, respectively. Several of the altered metabolites in host tissues were linked to the GABA shunt and glutaminolysis. Treatment of macrophages with GABA did not alter control of B. melitensis infection, and deletion of the putative GABA transporter BMEI0265 did not alter B. melitensis virulence. While glutaminolysis inhibition did not affect control of B. melitensis in macrophages, glutaminolysis was required for macrophage IL-1β production in response to B. melitensis. In sum, these results indicate that Brucella infection alters host tissue metabolism and that these changes could have effects on inflammation and the outcome of infection.
Insights
Brucella infection significantly alters host metabolism in mice, particularly impacting the GABA shunt and glutaminolysis pathways. These metabolic changes may influence inflammation and infection outcomes.
Area of Science:
- Microbiology
- Immunology
- Metabolomics
Background:
- Brucella is a gram-negative, facultative, intracellular bacterium posing significant risks to human and animal health.
- Brucella infection can manipulate host metabolism to enhance its replication and survival.
Purpose of the Study:
- To investigate tissue-specific metabolic alterations in mice infected with Brucella melitensis.
- To elucidate the role of specific metabolic pathways, such as the GABA shunt and glutaminolysis, in Brucella infection.
Main Methods:
- Murine infection model using Brucella melitensis.
- Gas chromatography-mass spectrometry (GC-MS) analysis of spleen, liver, and reproductive tract tissues.
- Macrophage-based experiments assessing the impact of GABA and glutaminolysis inhibition.
Main Results:
- Significant alterations in numerous metabolites were observed in reproductive tracts, spleens, and livers at two weeks post-infection.
- Altered metabolites were predominantly linked to the GABA shunt and glutaminolysis pathways.
- GABA treatment or deletion of a putative GABA transporter did not affect Brucella control or virulence, but glutaminolysis was essential for IL-1β production in macrophages.
Conclusions:
- Brucella infection profoundly impacts host tissue metabolism, with significant changes observed in reproductive tracts, spleens, and livers.
- While the GABA shunt appears less critical for Brucella virulence, glutaminolysis plays a key role in macrophage inflammatory responses.
- These metabolic shifts likely contribute to the overall pathogenesis and inflammatory outcome of Brucella infections.
