| Magnesium (Mg) is one of the most abundant metals in the human body, second only to
calcium. Mg is primarily stored in bones, but it is also present in human cells and tissues, where
it serves as a cofactor for numerous enzymatic reactions. Similarly, Mg also plays a vital role in
bacterial physiology, and it has been used in vitro as a substitute for manganese (Mn) in some
enzymes to sustain activity. For many bacterial pathogens like the major human upper
respiratory pathogen Streptococcus pneumoniae, the biological role for Mg is understudied. This
study investigates a role for Mg in Mn physiology for S. pneumoniae. We demonstrate that
mntE-null (ΔmntE) mutants, lacking the Mn-exporter, exhibit impaired growth due to
accumulation of Mn when exposed to elevated exogenous Mn. This Mn-sensitive growth
phenotype is rescued by exogenous Mg. Despite restoration of ΔmntE mutant growth to wildtype levels, we find that cell-associated Mn remains extremely elevated in ΔmntE cells.
Furthermore, microscopy analysis shows that ΔmntE cells are slightly more elongated and have
increased chaining, as well as cell lysis during Mg-treated Mn intoxication. These data findings
are consistent with ΔmntE cells experiencing Mn intoxication. We also find that exogenous Mg
can rescue the Mn-export deficient Escherichia coli ΔmntP strain from Mn intoxication to some
degree but can rescue growth of Mn-sensitive Bacillus subtilis ΔmntR. Together, these data
suggest that Mg may be interconnected with Mn physiology in S. pneumoniae and as such, have
potential implications in bacterial virulence and pathogenesis within the human host.
Keywords: Streptococcus, Bacteria, Manganese, Magnesium, Capsule |