title: 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.
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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, The Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
authors.forename: Lucy E
authors.initials: LE
authors.lastname: DesJardin
authors.forename: Jessica
authors.initials: J
authors.lastname: MacNeil
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kaufman
authors.forename: Beth
authors.initials: B
authors.lastname: Kutzbach
authors.forename: Rose
authors.initials: R
authors.lastname: Knaup
authors.forename: Travis R
authors.initials: TR
authors.lastname: McCarthy
authors.forename: Sudagar S
authors.initials: SS
authors.lastname: Gurcha
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Steven
authors.initials: S
authors.lastname: Clegg
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger