Abstract
The neurotransmitter gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the human brain; however, it is becoming more evident that this non-proteinogenic amino acid plays multiple physiological roles in biology. In the present study, the transport and function of GABA is studied in the highly infectious intracellular bacterium Brucella abortus. The data show that 3H-GABA is imported by B. abortus under nutrient limiting conditions and that the small RNAs AbcR1 and AbcR2 negatively regulate this transport. A specific transport system, gts, is responsible for the transport of GABA as determined by measuring 3H-GABA transport in isogenic deletion strains of known AbcR1/2 regulatory targets; however, this locus is unnecessary for Brucella infection in BALB/c mice. Similar assays revealed that 3H-GABA transport is uninhibited by the 20 standard proteinogenic amino acids, representing preference for the transport of 3H-GABA. Metabolic studies did not show any potential metabolic utilization of GABA by B. abortus as a carbon or nitrogen source, and RNA sequencing analysis revealed limited transcriptional differences between B. abortus 2308 with or without exposure to GABA. While this study provides evidence for GABA transport by B. abortus, questions remain as to why and when this transport is utilized during Brucella pathogenesis.
Highlights
Gamma-aminobutyric acid (GABA) is a non-proteinogenic amino acid that is a common and important inhibitory neurotransmitter in the vertebrate brain [1]
The transport and biological function of GABA was analyzed in the intracellular pathogen B. abortus
The data presented revealed that 3H-GABA is transported under nutrient limiting conditions, transport was regulated by the sRNAs AbcR1 and AbcR2, and transport occurred via an ABC-transport system homologous to the gts system in Rhizobium leguminosarum and A. tumefaciens
Summary
Gamma-aminobutyric acid (GABA) is a non-proteinogenic amino acid that is a common and important inhibitory neurotransmitter in the vertebrate brain [1]. Our understanding of the biological function of GABA has expanded over the years to include neurobiology, immunology, and bacteriology.
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