title: Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operon.
abstract: For successful colonization of the mammalian host, orally acquired bacteria must overcome the extreme acidic stress (pH < 2.5) encountered during transit through the host stomach. The glutamate-dependent acid resistance (GDAR) system is by far the most potent acid resistance system in commensal and pathogenic Escherichia coli, Shigella flexneri, Listeria monocytogenes and Lactococcus lactis. GDAR requires the activity of glutamate decarboxylase (GadB), an intracellular PLP-dependent enzyme which performs a proton-consuming decarboxylation reaction, and of the cognate antiporter (GadC), which performs the glutamatein /γ-aminobutyrateout (GABA) electrogenic antiport. Herein we review recent findings on the structural determinants responsible for pH-dependent intracellular activation of E. coli GadB and GadC. A survey of genomes of bacteria (pathogenic and non-pathogenic), having in common the ability to colonize or to transit through the host gut, shows that the gadB and gadC genes frequently lie next or near each other. This gene arrangement is likely to be important to ensure timely co-regulation of the decarboxylase and the antiporter. Besides the involvement in acid resistance, GABA production and release were found to occur at very high levels in lactic acid bacteria originally isolated from traditionally fermented foods, supporting the evidence that GABA-enriched foods possess health-promoting properties.
authors.affiliation: Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche, Sapienza Università di Roma, 04100, Latina, Italy. daniela.debiase@uniroma1.it
authors.forename: Daniela
authors.initials: D
authors.lastname: De Biase
authors.forename: Eugenia
authors.initials: E
authors.lastname: Pennacchietti
mesh_terms: D000143:Acids / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D023061:Gene Order; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D009876:Operon; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000143:Acids; D029968:Escherichia coli Proteins; C491226:GadC protein, E coli; D008565:Membrane Proteins; D005680:gamma-Aminobutyric Acid; C584507:gadB protein, E coli; D005968:Glutamate Decarboxylase