Fur-regulated MntH mediates metal homeostasis and immune evasion in Yersinia pseudotuberculosis
Year: 2026
Type: article
Abstract: During infection, host nutritional immunity restricts bacterial access to essential transition metals, in part through calprotectin (CP), a host metal-binding protein that sequesters manganese (Mn) and iron (Fe). However, whether the MntH transporter enables Yersinia pseudotuberculosis ( Yptb ) strain YPIII to withstand this CP-mediated metal restriction remains unclear. To address this question, we characterized the regulation and function of MntH in Yptb YPIII using molecular, genetic, physiological, and mouse-infection approaches. We found that MntH is a conserved member of the natural resistance-associated macrophage protein (Nramp) family whose expression is directly repressed by the ferric uptake regulator (Fur). Deletion of mntH reduced intracellular Mn and Fe accumulation, impaired bacterial growth under metal-limited conditions, and increased sensitivity to peroxide- and hydroxyl radical (HR)-associated stresses. In vitro, deletion of mntH impaired bacterial growth under CP-imposed metal restriction, and this defect was rescued by supplementation with Mn or Fe. In orally infected mice, the Δ mntH mutant yielded lower bacterial burdens in the feces and cecum, reduced competitive fitness, and milder cecal inflammation and liver damage than the wild-type strain. Notably, Yptb infection elevated cecal CP expression and depleted fecal Mn and Fe, whereas mntH expression was induced during infection, supporting a role for MntH in countering host-imposed metal limitation. Collectively, these findings establish Fur-regulated MntH as a key determinant of metal homeostasis, stress tolerance, and intestinal fitness in Yptb and provide insight into how this pathogen adapts to host nutritional limitation.
Source: Stress Biology
Institution: Northwest A&F University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225826359