Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Escherichia coli survives pH 2 acid stress at a level rivalling Helicobacter pylori. Of the three E. coli acid resistance systems involved, the one most efficient and most studied uses isozymes of glutamate decarboxylase (GadA/GadB) to consume intracellular protons, and a glutamate:gamma-amino butyric acid (GABA) anti-porter (GadC) to expel GABA in exchange for extracellular glutamate. Because acid resistance is a critical factor in resisting stomach acidity, mechanisms that control this system are extremely important. Here we show that an Era-like, molecular switch GTPase called TrmE regulates glutamate-dependent acid resistance. Western blot analysis revealed a TrmE-dependent, glucose-induced system and a TrmE-independent, glucose-repressed pathway. Gene fusion studies indicated that the TrmE requirement for GadA/B production takes place at both the transcriptional and translational levels. TrmE controls GAD transcription by affecting the expression of GadE, the essential activator of the gadA and gadBC genes. TrmE most probably controls gadE expression indirectly by influencing the synthesis or activity of an unknown regulator that binds the gadE control region. Translational control of GAD production by TrmE appears to be more direct, affecting synthesis of the decarboxylase and the anti-porter proteins. TrmE GTPase activity was critical for both the transcriptional and translational effects. Thus, TrmE is part of an increasingly complex control network designed to integrate diverse physiological signals and forecast future exposures to extreme acid. The significance of this network extends beyond acid resistance as the target of this control, GadE, regulates numerous genes in addition to gadA/BC.
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PMID:The Era-like GTPase TrmE conditionally activates gadE and glutamate-dependent acid resistance in Escherichia coli. 1552 79

The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues. However, the ECC was selected as a more practical delivery format for both packaging/shipping and vaccine administration ease. We have sought to increase Ty21a acid-resistance to allow for removal from the ECC and immune enhancement. To improve Ty21a acid-resistance, glutamate-dependent acid resistance genes (GAD; responsible for Shigella spp. survival at very low pH) were cloned on a multi-copy plasmid (pGad) under a controllable arabinose-inducible promoter. pGad enhanced acid survival of Ty21a by 5 logs after 3 hours at pH 2.5, when cells were pre-grown in arabinose and under conditions that promote an acid-tolerance response (ATR). For genetically 100% stable expression, we inserted the gad genes into the Ty21a chromosome, using a method that allowed for subsequent removal of a selectable antibiotic resistance marker. Further, both bacterial growth curves and survival assays in cultured human monocytes/macrophages suggest that neither the genetic methods employed nor the resulting acid-resistance conferred by expression of the Gad proteins in Ty21a had any effect on the existing attenuation of this vaccine strain.
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PMID:Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery. 2767 28

Fruit acidity is an important determinant of peach organoleptic quality, but its regulatory mechanism remains elusive. Measurement of organic acids in ripe fruits of seventy-five peach cultivars revealed the predominant components malate and citrate, accompanied by quinate. Organic acid accumulation increased at early stages of fruit growth, but exhibited a more dramatic reduction in low-acid cultivar during later stages of fruit development compared to high-acid cultivars. Low-acid cultivars showed citrate degradation and less transport of malate into the vacuole due to up- and down-regulation of a GABA pathway gene GAD and a malate transporter gene ALMT9, respectively. The NAD-MDH1 gene might control the rate-limiting step in malate synthesis, while three genes, PDK, PK, and ADH, could affect citrate synthesis through the pyruvate-to-acetyl-CoA-to-citrate pathway. Altogether, these results suggested that malate accumulation is controlled at the level of metabolism and vacuolar storage, while metabolism is crucial for citrate accumulation in peach.
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PMID:Assessment of organic acid accumulation and its related genes in peach. 3270 62