Inactivation of Mycobacterium tuberculosis mannosyltransferase pimB reduces the cell wall lipoarabinomannan and lipomannan content and increases the rate of bacterial-induced human macrophage cell death

JB Torrelles, LE DesJardin, J MacNeil, TM Kaufman, B Kutzbach, R Knaup, TR McCarthy, Sudagar Gurcha, Gurdyal Besra, S Clegg, LS Schlesinger

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The Mycobacterium tuberculosis (M.tb) cell wall contains an important group of structurally related mannosylated lipoglycans called phosphatidyl-myo-inositol mannosides (PIMs), lipomannan (LM), and mannose-capped lipoarabinomannan (ManLAM), where the terminal alpha-[1 -> 2] mannosyl structures on higher order PIMs and ManLAM have been shown to engage C-type lectins such as the macrophage mannose receptor directing M.tb phagosome maturation arrest. An important gene described in the biosynthesis of these molecules is the mannosyltransferase pimB (Rv0557). Here, we disrupted pimB in a virulent strain of M.tb. We demonstrate that the inactivation of pimB in M.tb does not abolish the production of any of its cell wall mannosylated lipoglycans; however, it results in a quantitative decrease in the ManLAM and LM content without affecting higher order PIMs. This finding indicates gene redundancy or the possibility of an alternative biosynthetic pathway that may compensate for the PimB deficiency. Furthermore, infection of human macrophages by the pimB mutant leads to an alteration in macrophage phenotype concomitant with a significant increase in the rate of macrophage death.
Original languageEnglish
Pages (from-to)743-755
Number of pages13
JournalGlycobiology
Volume19
Issue number7
DOIs
Publication statusPublished - 1 Jul 2009

Keywords

  • lipoarabinomannan
  • macrophage death
  • mannosyltransferase
  • phosphatidyl-myo-inositol mannoside
  • Mycobacterium tuberculosis

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