ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Magnesium modulates the stress response of oral streptococci to environmental and antibiotic challenges by altering cell envelope and nutrient transport pathways
Provisionally accepted
- Indiana University Indianapolis, Indianapolis, United States
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ABSTRACT Background Magnesium (Mg2+) is one of the most abundant metals in human teeth, second only to calcium. Demineralization of the tooth, caused by sugar intake or acid reflux, releases Mg2+ into the saliva. Mg2+ is also recommended as a dietary supplement for the prevention and treatment of chronic diseases. Oral streptococci, therefore, must regulate Mg2+ homeostasis to adapt to fluctuating levels of saliva in the human oral cavity. Materials and Methods We determined the toxic concentration of MgCl2 for Streptococcus spp. and used a sub-toxic dose to assess its effect on osmotic and cation-excess stress tolerance. Growth assays, ICP-MS, proteomic analysis, and lipidomic analysis were performed on wild-type and mutant strains lacking a putative Mg2+ efflux pump homolog. Results Mg²⁺ supplementation enhanced tolerance to osmotic and cation-excess stress in both caries-associated and commensal streptococci. Homologs of the magnesium protection factor A (MpfA) were found across Streptococcus groups. Mutants lacking mpfA homologs (smu_1693 in S. mutans, and ssa1761 in S. sanguinis) showed MgCl2 sensitivity. Despite unchanged intracellular Mg2+ levels in Δsmu_1693, the mutant exhibited stress tolerance, consistent with the disruption of magnesium efflux pumps. Proteomic and lipidomic analyses revealed altered levels of amino acid transporters, cell envelope proteins, and an increase in long-chain unsaturated fatty acids. Furthermore, modulating intracellular Mg2+ concentration, either by MgCl2 supplementation or by eliminating HlyX, impacted the efficacy of multiple cell wall-targeting antibiotics. Conclusion 3 This study highlights the role of Mg2+ in enhancing stress tolerance and modulating antibiotic sensitivity in streptococci, using S. mutans as a model.
Keywords: Magnesium, Oral streptococci, Streptococcus mutans, efflux pump, HlyX
Received: 18 Jul 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Mishra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Surabhi Mishra, sumishr@iu.edu
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