title: The external PASTA domain of the essential serine/threonine protein kinase PknB regulates mycobacterial growth.
abstract: PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results in delayed regrowth, accumulation of elongated bacteria and increased sensitivity to β-lactam antibiotics. These changes are accompanied by altered production of certain enzymes involved in cell-wall biosynthesis as revealed by proteomics studies. The growth inhibition caused by overexpression of the PknB_PASTA domain is completely abolished by enhanced concentration of magnesium ions, but not muropeptides. Finally, we show that the addition of recombinant PASTA domain could prevent regrowth of Mycobacterium tuberculosis, and therefore offers an alternative opportunity to control replication of this pathogen. These results suggest that the PknB_PASTA domain is involved in regulation of peptidoglycan biosynthesis and maintenance of cell-wall architecture.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Obolbek
authors.initials: O
authors.lastname: Turapov
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Loraine
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Jenkins
authors.affiliation: Centre de Biochimie Structurale, CNRS UMR 5048, 29, rue de Navacelles, Montpellier 34090, France INSERM U1054, Université Montpellier I et II, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthe
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: McFeely
authors.affiliation: Dipartimento di BioScienze, Università degli Studi di Milano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Forti
authors.affiliation: Dipartimento di BioScienze, Università degli Studi di Milano, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ghisotti
authors.affiliation: Department of Chemistry and Biochemistry, 423 Nieuwland Science Center, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Dusan
authors.initials: D
authors.lastname: Hesek
authors.affiliation: Department of Chemistry and Biochemistry, 423 Nieuwland Science Center, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Mijoon
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Bottrill
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.affiliation: Department of Chemistry and Biochemistry, 423 Nieuwland Science Center, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
authors.affiliation: Centre de Biochimie Structurale, CNRS UMR 5048, 29, rue de Navacelles, Montpellier 34090, France INSERM U1054, Université Montpellier I et II, Montpellier, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen-Gonsaud
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK gvm4@le.ac.uk.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Mukamolova
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D047090:beta-Lactams; C475060:PknB protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases
keywords: Mycobacterium tuberculosis; PASTA domain; PknB; magnesium; muropeptides; serine/threonine protein kinase