Calcium Rescues Streptococcus pneumoniae D39 ΔmntE Manganese-Sensitive Growth Phenotype

Calcium (Ca²⁺) functions as a universal signal messenger in eukaryotes but in bacteria, the physiological roles for Ca²⁺ are limited. Here, we examine the role of Ca²⁺ in Streptococcus pneumoniae during manganese (Mn²⁺) intoxication. S. pneumoniae mntE mutants, lacking the Mn²⁺ efflux transporter, exhibit impaired growth due to accumulation of Mn²⁺ when exposed to elevated exogenous Mn²⁺. This Mn²⁺-sensitive growth defect is restored to wild-type growth level by exogenous Ca²⁺, in a Ca²⁺-dependent manner. Despite growth restoration of the mntE mutant to wild-type levels, cellular Mn²⁺ remains elevated in this strain. Bacterial capsule production is also increased for the mntE mutant, resulting in reduced adherence capacity to surfaces and poor biofilm formation, which is consistent with it experiencing Mn²⁺ intoxication. Ca²⁺ presence did not significantly impact bacterial capsule production or biofilm formation. Further analysis of the cell morphology demonstrates that Ca²⁺ contributes to cell division and reduces cell chain lengths. Together, these data describe the first role of Ca in S. pneumoniae that has potential implications in bacterial virulence since Ca affects cell division and likely Mn²⁺-associated cellular processes.