title: Disruption of the serine/threonine protein kinase H affects phthiocerol dimycocerosates synthesis in Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis possesses a complex cell wall that is unique and essential for interaction of the pathogen with its human host. Emerging evidence suggests that the biosynthesis of complex cell-wall lipids is mediated by serine/threonine protein kinases (STPKs). Herein, we show, using in vivo radiolabelling, MS and immunostaining analyses, that targeted deletion of one of the STPKs, pknH, attenuates the production of phthiocerol dimycocerosates (PDIMs), a major M. tuberculosis virulence lipid. Comparative protein expression analysis revealed that proteins in the PDIM biosynthetic pathway are differentially expressed in a deleted pknH strain. Furthermore, we analysed the composition of the major lipoglycans, lipoarabinomannan (LAM) and lipomannan (LM), and found a twofold higher LAM/LM ratio in the mutant strain. Thus, we provide experimental evidence that PknH contributes to the production and synthesis of M. tuberculosis cell-wall components.
authors: Department of Medicine, Division of Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors: Anaximandro
authors: A
authors: Gómez-Velasco
authors: Department of Medicine, Division of Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors: Horacio
authors: H
authors: Bach
authors: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Amrita K
authors: AK
authors: Rana
authors: School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Liam R
authors: LR
authors: Cox
authors: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Apoorva
authors: A
authors: Bhatt
authors: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Gurdyal S
authors: GS
authors: Besra
authors: Department of Medicine, Division of Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors: Yossef
authors: Y
authors: Av-Gay
mesh_terms: D002460:Cell Line; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D008055:Lipids; C008901:phthiocerol dimycocerosate; D017346:Protein Serine-Threonine Kinases