How Pathogens Feel and Overcome Magnesium Limitation When in Host Tissues

Abstract

Host organisms utilize nutritional immunity to limit the availability of nutrients essential to an invading pathogen. Nutrients may include amino acids, nucleotide bases, and transition metals, the essentiality of which varies among pathogens. The mammalian macrophage protein Slc11a1 (previously Nramp1) mediates resistance to several intracellular pathogens. Slc11a1 is proposed to restrict growth of Salmonella enterica serovar Typhimurium in host tissues by causing magnesium deprivation. This is intriguing because magnesium is the most abundant divalent cation in all living cells. A pathogen's response to factors such as Slc11a1 that promote nutritional immunity may therefore reflect what the pathogen 'feels' in its cytoplasm, rather than the nutrient concentration in host cell compartments. HighlightsNutritional immunity is a host defense mechanism that limits nutrient availability to an invading pathogen.

Genomic Characterization of Salmonella enterica serovar Weltevreden Associated with Human Diarrhea

“…These VFGs encoded proteins participate in bacterial adherence, magnesium uptake, resistance to antimicrobial peptides, serum resistance, anti-stress, toxin, etc. All these bioactivities are beneficial for bacterial survival and fitness in hosts and therefore contribute to the pathogenesis ( 37 ).…”

Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis

“…This suggests that a macrophage-induced stress, other than Mg 2+ starvation, impairs Salmonella translation, mimicking a physiological signal experienced during cytoplasmic Mg 2+ starvation. That is, when inside macrophages, Salmonella may "sense" cytoplasmic Mg 2+ starvation even though Mg 2+ may not be limiting in the subcellular compartment harboring Salmonella (60).…”

The role of hypoxia‐inducible factor 1‐alpha in inflammatory bowel disease

“…However, in cultured macrophages, HIF‐1α mediated the increase in Wnt1 expression induced by hypoxia, which enhanced protein levels of β‐catenin, activated mTOR, and decreased autophagy in epithelial cells in coculture (Ortiz‐Masia et al, 2014). The macrophage protein Slc11a1/Nramp1 has an important role in infectious and inflammatory diseases, including rheumatoid arthritis, IBD, and tuberculosis (Blanc‐Potard & Groisman, 2021). Targeted HIF‐1α ablation in murine macrophages attenuated Slc11a11 expression which is due to HIF‐1α regulates allelic variation in SLC11A1 expression by directly binding to the microsatellite (Bayele et al, 2007).…”