Exploring the function of novel arginine phosphorylation in streptococcal physiology

ABSTRACT Post-translational modification (PTM) by phosphorylation plays an important role in protein folding, stability, and function. In bacteria, protein phosphorylation plays a key role in bacterial physiology and virulence gene regulation (pathogenesis) by participating in signal sensing and transduction networks. Protein phosphorylation occurs predominantly on six amino acids, and they form different chemical bonds. Phosphorylation of serine, threonine, and tyrosine residues forms a stable ester bond. Phosphorylation of aspartate and histidine forms a relatively unstable phosphoramidate P-N bond. These two types of phosphorylation are predominantly involved in signal transduction and gene regulation. On the other hand, phosphorylation of the arginine residue (Arg) is a novel mode of PTM recently discovered in Bacillus subtilis, Staphylococcus aureus, and Mycolibacterium smegmatis. In these organisms, Arg phosphorylation occurs in >100 different proteins and is involved in protein quality control, translational, and transcriptional regulations. Despite the importance in the bacterial physiology, nothing is known about Arg phosphorylation in Streptococcus, a medically important genus. We found that in Streptococcus mutans, a dental pathogen, Arg-phosphorylation occurs; however, the homolog of the B. subtilis and S. aureus Arg-kinase (McsB) is conspicuously absent in streptococci. The major goals of this study are to understand the physiological role of Arg-phosphorylation in S. mutans and to identify the putative kinase enzyme responsible for Arg-phosphorylation in streptococci.