title: 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. Although 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 have been 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 of the domains, including the 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 that the continued presence of PstP is necessary for pathogen survival. Taken together, our data suggest an important role for PstP in establishing and maintaining infection, possibly via the modulation of cell division events.
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.|the Academy of Scientific and Innovative Research (AcSIR), CSIR-IGIB, Delhi-110025, India.
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: From the National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Arora
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
authors.forename: Lalit K
authors.initials: LK
authors.lastname: Singh
authors.affiliation: the Department of Zoology, University of Delhi Delhi-110007, India.
authors.forename: Aakriti
authors.initials: A
authors.lastname: Gangwal
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
authors.forename: Andaleeb
authors.initials: A
authors.lastname: Sajid
authors.affiliation: the Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS, UMR 5235, Montpellier, France, and.
authors.forename: Virginie
authors.initials: V
authors.lastname: Molle
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India, ysingh@igib.res.in.|the Department of Zoology, University of Delhi Delhi-110007, India.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.affiliation: From the National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India, vinaykn@nii.ac.in.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Nandicoori
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D017353:Gene Deletion; D051379:Mice; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010749:Phosphoprotein Phosphatases
keywords: Mycobacterium tuberculosis; PstP; cell division; cell signaling; mycobacteria; phosphatase; phosphorylation; protein serine/threonine phosphatase (PSP)