Serine/threonine protein phosphatase PstP of Mycobacterium tuberculosis is necessary for accurate cell division and survival of pathogen

Abstract

Protein phosphatases play vital roles in phosphorylation-mediated cellular signaling. While there are 11 serine/threonine protein kinases in Mycobacterium tuberculosis, only one serine/threonine phosphatase, PstP, has been identified. Although PstP has been biochemically characterized and multiple in vitro substrates identified, its physiological role has not yet been elucidated. In this study we have investigated the impact of PstP on cell growth and survival of the pathogen in the host. Overexpression of PstP led to elongated cells and partially compromised survival. We find that depletion of PstP is detrimental to cell survival, eventually leading to cell death. PstP depletion results in elongated multiseptate cells, suggesting a role for PstP in regulating cell division events. Complementation experiments performed with PstP deletion mutants revealed marginally compromised survival, suggesting that all the domains including extracellular domain are necessary for complete rescue. On the other hand, the catalytic activity of PstP is absolutely essential for the in vitro growth. Mice infection experiments establish a definitive role for PstP in pathogen survival within the host. Depletion of PstP from established infections causes pathogen clearance, indicating the continued presence of PstP is necessary for pathogen survival. Taken together, our data suggests an important role for PstP in establishing and maintaining infection, possibly via the modulation of cell division events.