Streptococcus pneumoniae is a major human pathogen responsible for significant mortality and morbidity worldwide. Within the annotated genome of the pneumococcus lies a previously uncharacterized protein tyrosine phosphatase which shows homology to low molecular weight protein tyrosine phosphatases (LMWPTPs). LMWPTPs modulate many processes critical for the pathogenicity of a number of bacteria including capsular polysaccharide biosynthesis, stress response and persistence in host macrophages. Here, we demonstrate that Spd1837 is indeed a LMWPTP, by purifying the protein, and characterizing its phosphatase activity. Spd1837 showed specific tyrosine phosphatase activity, and it did not form higher order oligomers in contrast to many other LMWPTPs. Substrate-trapping assays using the wild-type and the phosphatase-deficient Spd1837 identified potential substrates/interacting proteins including major metabolic enzymes such as ATP-dependent-6-phosphofructokinase and Hpr kinase/phosphorylase. Given the tight association between the bacterial basic physiology and virulence, this study hopes to prompt further investigation of how the pneumococcus controls its metabolic flux via the LMWPTP Spd1837.
Keywords: Streptococcus pneumoniae; low molecular weight phosphatase; phosphatase substrates identification; pneumococcus; tyrosine phosphorylation.