The five homologous CiaR-controlled sRNAs modulate Streptococcus pneumoniae Zn-resistance
Zn and Mn are essential micronutrients for many bacteria including Streptococcus pneumoniae. While Zn performs vital structural or catalytic roles in certain proteins, in excess, Zn can inhibit Mn uptake by S. pneumoniae and displace, but not functionally replace Mn from key enzymes including superoxide dismutase A (SodA). Here, we show that the Ccn small regulatory RNAs promote S. pneumoniae Mn uptake and resistance to the oxidative stress. Furthermore, we demonstrate that these small regulatory RNAs modulate the ability of S. pneumoniae to cause invasive pneumonia. Altogether, these findings reveal a new layer of regulation of S. pneumoniae Zn and Mn homeostasis and suggest that there are factors in addition to known transporters that modulate intracellular Mn levels. Overall design: Characterization of the five homologous Ccn sRNAs in Streptococcus pneumoniae D39 using RNA-seq. Gene expression of  S. pneumoniae strain D39, TIGR4,  and its derived ccnABCDE mutants grown in BHI broth alone or supplemented with 0.2 mM ZnSO4 was determined by RNA-seq using biological triplicates.