mnth

MntH is the manganese transporter protein encoded by the mntH gene in many bacteria and some archaea. It belongs to the Nramp (natural resistance-associated macrophage protein) family of divalent metal ion transporters and functions as a proton-coupled transporter that imports Mn2+ from the extracellular or periplasmic space into the cytoplasm. In several species, MntH can also allow uptake of other divalent cations under certain conditions, reflecting a broader but substrate-biased specificity.

Structure and mechanism: MntH proteins typically contain multiple transmembrane helices and operate by coupling the downhill flow of protons to the transport of divalent metals. They are thought to use the proton motive force rather than ATP directly. Substrate specificity and transport kinetics vary among species; Mn2+ uptake is physiologically important for metal homeostasis, oxidative stress defense, and enzyme function. Expression is often regulated by cellular Mn availability via metal-sensing regulators.

Biological role: In bacteria, Mn imported by MntH supports manganese-dependent enzymes such as Mn-dependent superoxide dismutases and ribonucleotide reductases. Limiting Mn uptake through MntH can reduce virulence in several pathogens and alter resistance to oxidative stress. In some organisms, MntH and other Nramp transporters provide redundant pathways for metal acquisition, ensuring survival in metal-limited environments.

Distribution and regulation: MntH homologs are widespread in Gram-positive and Gram-negative bacteria and some archaea. Regulation is context-dependent, with Mn-responsive regulators such as MntR or Fur or DtxR modulating transcription in response to intracellular Mn or Fe status. In pathogenic species, MntH is a factor in host colonization and immune evasion.

Relation to eukaryotes: The NRAMP family is functionally conserved across domains, and mammalian Nramp/DMT1 transporters mediate uptake of iron and other metals, but the bacterial MntH represents a distinct, often proton-coupled transporter adapted to prokaryotic physiology.