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Status |
Public on Aug 07, 2021 |
Title |
Transcriptomics reveal strain-specific metabolic strategies for acid resistance and gamma-aminobutyric acid (GABA) production in Levilactobacillus brevis. |
Organism |
Levilactobacillus brevis |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Background: Of the many neurotransmitters in humans, gamma-aminobutyric acid (GABA) shows potential for improving several mental health indications such as stress and anxiety. The microbiota-gut-brain axis is an important pathway for GABAergic effects, as microbially-secreted GABA within the gut can affect host mental functionhealth outcomes. Understanding the molecular characteristics of GABA production by microbes within the gut can offer insight to novel therapies for mental health. Results: Three strains of Levilactobacillus brevis with syntenous glutamate decarboxylase (GAD) operons were evaluated for overall growth, glutamate utilization, and GABA production in typical synthetic growth media supplemented with monosodium glutamate (MSG). Levilactobacillus brevis Lbr-6108 (Lbr-6108) and Levilactobacillus brevis Lbr-35 (Lbr-35) had similar growth profiles but differed significantly in GABA secretion and acid resistance. Lbr-6108 produced GABA early, within the growth phase, and produced significantly more GABA than Lbr-35 and the type strain Levilactobacillus brevis ATCC 14689 after the stationary phase. The global gene expression during GABA production was determined by RNA sequencing at several timepoints. The GAD operon, responsible for GABA production and secretion, activated in Lbr-6108 after only six hours of fermentation and continued throughout the stationary phase. Furthermore, Lbr-6108 activated many different acid resistance mechanisms concurrently, which contribute to acid tolerance and energy production. In contrast, Lbr-35, which has a genetically similar GAD operon, including two copies of the GAD gene, showed no upregulation of the GAD operon, even when cultured with MSG. Conclusions: This study is the first to evaluate whole transcriptome changes in L. brevis during GABA production over multiple timepoints. The concurrent expression of multiple acid-resistance mechanisms reveals niche-specific metabolic functionality between common human commensals and highlights the complex regulation of GABA metabolism in this important microbial species. Furthermore, the increased and rapid GABA production of Lbr-6108 highlights the strain’s potential as a therapeutic and the overall value of screening microbes for effector molecule output.
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Overall design |
Gene expression of Lbr-35 and Lbr-6108 timeseries grown in media with and without additional monosodium glutamate.
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Contributor(s) |
Morovic W, Gerdes S, Nedveck D, Zabel B, Poore M |
Citation(s) |
34488774 |
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Submission date |
Aug 05, 2021 |
Last update date |
Sep 15, 2021 |
Contact name |
Bryan Zabel |
E-mail(s) |
bryan.zabel@iff.com
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Organization name |
International Flavors & Fragrances Inc
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Department |
GEM
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Street address |
3329 Agriculture Dr
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City |
Madison |
State/province |
wi |
ZIP/Postal code |
53716 |
Country |
USA |
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Platforms (1) |
GPL30477 |
Illumina HiSeq 4000 (Levilactobacillus brevis) |
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Samples (40)
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Relations |
BioProject |
PRJNA752280 |
SRA |
SRP331192 |
Supplementary file |
Size |
Download |
File type/resource |
GSE181504_Lactobacillus_brevis_DPC_6108_public_June2020.gff.gz |
70.5 Kb |
(ftp)(http) |
GFF |
GSE181504_Lactobacillus_brevis_Lbr-35_1580.364.gff.gz |
58.2 Kb |
(ftp)(http) |
GFF |
GSE181504_lbr35-normalized-counts-matrix.csv.gz |
339.8 Kb |
(ftp)(http) |
CSV |
GSE181504_lbr6108-normalized-counts-matrix.csv.gz |
417.3 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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