C4-Dicarboxylate Transport Mechanisms in Bacterial Systems

Bacteria utilise C4-dicarboxylates—including succinate, fumarate and malate—as key intermediates in central carbon metabolism, energy production and environmental sensing. Uptake across the cytoplasmic membrane is achieved by specialised transport proteins that harness electrochemical gradients, often the proton motive force, to drive concentrative import. In Gram-negative species, a periplasmic dicarboxylate-binding protein delivers substrate to an outer membrane porin and to an inner membrane symporter, while Gram-positive bacteria exploit inducible permeases with high specificity for malate or fumarate. Regulation of these transport pathways is tightly linked to global stress regulators and second messengers such as c-di-GMP, ensuring that dicarboxylate uptake supports respiration under both fermentative and aerobic conditions. Understanding these systems is crucial for improving microbial production processes, modulating gut microbiota interactions and targeting pathogenic bacteria that rely on dicarboxylate scavenging for virulence.

Research from Nature Portfolio

A study of extraintestinal pathogenic Escherichia coli revealed that loss of the global stress regulator RpoS enables aerobic citrate utilisation in the presence of glucose, a trait absent in wild-type strains. RpoS inactivation induces expression of the citrate transporter CitT, which in turn mediates ferric citrate uptake. Concurrently, pathoadaptive mutations affecting c-di-GMP phosphodiesterase activity adjust surface adhesion and metabolic capacity, linking second-messenger signalling to dicarboxylate transport. These findings illuminate how modulation of global stress responses reshapes transporter repertoires, permitting adaptation to new ecological niches and nutrient sources.

C4-Dicarboxylate Transport Mechanisms in Bacterial Systems publication trend

The graph below shows the total number of articles in c4-dicarboxylate transport mechanisms in bacterial systems across all publications each year (not limited to Nature Index journals).

Technical terms

C4-dicarboxylate: Molecule with four carbons and two carboxylate groups (succinate, fumarate, malate).

Dct system: High-affinity, proton-driven transport machinery for C4-dicarboxylates in bacteria.

DBP: Periplasmic dicarboxylate-binding protein that delivers substrate to membrane channels.

Porin: Outer membrane channel protein that permits passive diffusion of small solutes.

Proton motive force: Electrochemical gradient of protons across a membrane used to power secondary transport.

c-di-GMP: Cyclic diguanylate monophosphate, a bacterial second messenger controlling biofilm formation and transporter expression.

CitT: Inner membrane carrier that exchanges citrate (a C6-dicarboxylate) and related anions in Escherichia coli, regulated by global stress factors.

References

1. Absence of Global Stress Regulation in Escherichia coli Promotes Pathoadaptation and Novel c-di-GMP-dependent Metabolic Capability. Scientific Reports (2019).
2. Transport of Succinate in Escherichia coli I. BIOCHEMICAL AND GENETIC STUDIES OF TRANSPORT IN WHOLE CELLS. Journal of Biological Chemistry (1972).
3. Transport of Dicarboxylic Acids in Bacillus subtilis INDUCIBLE UPTAKE OF l-MALATE. Journal of Biological Chemistry (1972).
4. Use of a nonpenetrating substrate analogue to study the molecular mechanism of the outer membrane dicarboxylate transport system in Escherichia coli K12.. Journal of Biological Chemistry (1981).