Functional Systems

AADB organizes microbial pH-resistance genes into 11 mechanism-oriented functional systems to support browsing, interpretation, and comparative analysis.

Functional Systems Summary

The table below summarizes the functional systems currently represented in AADB, their one-line mechanism definitions, representative genes, and primary stress context.

These system definitions are used as an organizing framework for AADB curation and browsing. They are mechanism-linked categories rather than mutually exclusive biological compartments, and a single protein may contribute to multiple pH-related processes.

System One-line Definition Representative Genes Primary Stress Context
1. Glutamate Decarboxylase (GAD) System Proton consumption coupled to amino acid/amine exchange gadA, gadB, gadC, gadE, evgS/evgA Acidic (pH 2.5–4.0)
2. Antiporter System Regulate proton flux via cation/H+ exchange nhaA, nhaB, chaA, ybaT, mrp complex Acid and alkali
3. Acid-Activated Chaperone System Stabilize periplasmic proteins under low pH HdeA, HdeB, HdeD Extremely acidic (pH 2.0–3.0)
4. Alkaline Resistance System Support cytoplasmic pH maintenance at high external pH pha, sigB Alkaline (pH 8.0–10.0)
5. pH Response Regulatory System Two-component signaling and pH-linked transcriptional control evgS/evgA, gadE, cadC, ydeO, rpoS Broad pH range
6. General Stress Response System Provide cross-protection under pH extremes groEL/groES, dnaK/dnaJ, clpP, recA, uvrAB Acidic/alkaline stress
7. Periplasmic pH Regulation System Urease-linked buffering in host-associated niches ureI, carbonic anhydrase Neutral to acidic (gastric/host)
8. Membrane pH Transport System Primary/secondary transport affecting intracellular pH F1F0-ATPase, NDH-1 Broad pH range (shock response)
9. Glutaminase System Generate ammonia and couple to decarboxylation-based resistance ybaS (glsA), acid-activated glutaminase Neutral to alkaline
10. Urease-Mediated Neutralization System Buffer extreme acidity via ammonia production ureA, ureB, ureC, ureI Gastric acid (pH 1.0–3.0)
11. Other pH-Related Mechanisms Other curated pH-related mechanisms for coverage adiA/adiC, cadA/cadB/cadC, speF/potE, arcABC Various (mostly acid)

Mechanism summary: The GAD system consumes protons through glutamate decarboxylation coupled to amino acid/amine exchange. Critical for survival in strongly acidic environments (pH ~2–3).

Representative genes: gadA, gadB, gadC, gadE, evgS/evgA

Typical organisms: E. coli, intestinal bacteria

Stress context: Acidic (pH 2.5–4.0)

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Mechanism summary: Antiporter systems regulate proton flux via cation/H+ exchange. Membrane transporters exchange ions for protons to maintain pH homeostasis.

Representative genes: nhaA, nhaB, chaA, ybaT, mrp complex

Typical organisms: Gram-negative bacteria

Stress context: Acid and alkali (critical in alkali)

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Mechanism summary: Acid-activated chaperones stabilize periplasmic proteins under low pH. HdeA and HdeB are inactive at neutral pH but become activated by acid-induced structural changes.

Representative genes: HdeA, HdeB, HdeD

Typical organisms: E. coli, intestinal bacteria

Stress context: Extremely acidic (pH 2.0–3.0)

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Mechanism summary: Alkaline-resistance modules support cytoplasmic pH maintenance at high external pH. Strategies include Na+/H+ antiporters and cell envelope modifications.

Representative genes: pha, sigB

Typical organisms: Environmental bacteria

Stress context: Alkaline (pH 8.0–10.0)

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Mechanism summary: pH-response regulatory programs include two-component signaling and pH-linked transcriptional control. Bacteria sense pH changes and trigger adaptive gene expression.

Representative genes: evgS/evgA, gadE, cadC, ydeO, rpoS

Typical organisms: Various bacteria

Stress context: Broad pH range

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Mechanism summary: General stress response modules provide cross-protection under pH extremes. The RpoS regulon orchestrates DNA repair, chaperones, and proteases.

Representative genes: groEL/groES, dnaK/dnaJ, clpP, recA, uvrAB

Typical organisms: Various bacteria

Stress context: Acidic/alkaline stress

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Mechanism summary: Periplasmic pH regulation includes urease-linked buffering in host-associated niches. H. pylori uses urease to create a buffered microenvironment (pH ~6) when external pH is ~1–2.

Representative genes: ureI, carbonic anhydrase

Typical organisms: Pathogenic bacteria (e.g., H. pylori)

Stress context: Neutral to acidic (gastric/host)

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Mechanism summary: Membrane pH transport includes primary/secondary transport processes affecting intracellular pH. F1F0-ATPase can reverse operation under acid stress to expel H+.

Representative genes: F1F0-ATPase, NDH-1

Typical organisms: Various bacteria

Stress context: Broad pH range (shock response)

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Mechanism summary: Glutaminase-dependent buffering generates ammonia and couples to decarboxylation-based resistance. Acid-activated glutaminase (YbaS/GlsA) produces ammonia and glutamate.

Representative genes: ybaS (glsA), acid-activated glutaminase

Typical organisms: E. coli, intestinal bacteria

Stress context: Neutral to alkaline

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Mechanism summary: Urease-mediated neutralization buffers extreme acidity via ammonia production. Urease hydrolyzes urea into ammonia, which neutralizes acid. H. pylori maintains periplasmic pH ~6 when external pH is ~1–2.

Representative genes: ureA, ureB, ureC, ureI

Typical organisms: H. pylori, gastric bacteria

Stress context: Gastric acid (pH 1.0–3.0)

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Mechanism summary: Other curated pH-related mechanisms retained for coverage and hypothesis generation. Includes alternative amino acid decarboxylase systems (arginine, lysine, ornithine) and the arginine deiminase (ADI) pathway.

Representative genes: adiA/adiC, cadA/cadB/cadC, speF/potE, arcABC

Typical organisms: Various

Stress context: Various (mostly acid)

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