Bacterial Mg2+ Homeostasis, Transport, and Virulence Original paper

What was reviewed?

This paper reviewed how bacteria keep magnesium (Mg2+) at workable levels and why that control matters for infection. It explained Mg2+ as a structural and enzymatic necessity that stabilizes membranes and ribosomes, neutralizes nucleic acids, and supports many reactions, so bacteria must actively maintain Mg2+ in different compartments. The review focused on how bacteria sense Mg2+ outside the cytoplasm versus inside it, how they adjust Mg2+ transporter expression and activity, and how they remodel the cell envelope to cope when Mg2+ is scarce. It used Salmonella as the best-characterized model system and then extended the logic to other pathogens and regulatory circuits.

Who was reviewed?

The authors reviewed bacterial systems rather than human participants, so the “who” here was a set of bacterial species and their molecular pathways. The centerpiece was Salmonella enterica serovar Typhimurium because it has the strongest mechanistic evidence for Mg2+ transport and Mg2+-sensing regulation, including multiple transporters and distinct sensors for extra- and intracellular Mg2+. The review also pulled in other gram-negative bacteria with related PhoP/PhoQ signaling and virulence phenotypes, and it discussed gram-positive Group A Streptococcus as an example of a different Mg2+-responsive two-component system that primarily controls virulence genes. Across these organisms, the reviewed “subjects” were transport proteins, two-component regulators, RNA-based Mg2+ sensors, and envelope modification enzymes that change how bacteria manage cation stress.

What were the most important findings?

Mg2+ limitation is not just a nutrient issue for bacteria, but a signal that switches on virulence programs and survival mechanisms. Bacteria sense low extracytoplasmic Mg2+ through sensor kinases like PhoQ in Salmonella, which then drives PhoP-dependent transcription of genes that help survival under low Mg2+, including Mg2+ transporters and envelope remodeling functions. In parallel, bacteria sense cytoplasmic Mg2+ using RNA leaders (riboswitch-like sensors) that control whether transcription continues into Mg2+ transporter coding regions, so the cell stops making high-cost uptake systems once internal Mg2+ is adequate. The review highlighted three major Mg2+ transporter classes—CorA, MgtE, and the ATP-driven MgtA/MgtB family, and explained why multiple transporters exist: they differ in energy source, temperature performance, inhibitor sensitivity, and function under changing membrane potential. A key virulence connection was that low Mg2+ and host-like stresses converge on these regulatory systems, and some Mg2+ transport and sensing modules sit within pathogenicity islands

What are the greatest implications of this review?

For clinicians and microbiome translation, the implication is that host environments can shape microbial community behavior by restricting Mg2+ and by applying linked pressures such as acidity and antimicrobial peptides, and these pressures can directly push pathogens toward virulence states. This makes Mg2+ availability a plausible mechanistic bridge between mucosal inflammation and pathogen expansion, because the same signals that reflect host defense can activate bacterial regulatory circuits that improve survival and tissue damage potential. It also suggests that interventions that alter luminal ionic conditions, peptide stress, or inflammation could change pathogen fitness even without directly “killing” microbes, and that Mg2+-responsive pathways may serve as targets for anti-virulence strategies that reduce infection severity without relying solely on antibiotics.