Glycobiology Advance Access published online on March 24, 2009
Glycobiology, doi:10.1093/glycob/cwp042
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Inactivation of Mycobacterium tuberculosis mannosyltransferase pimB reduces cell wall lipoarabinomannan and lipomannan content and increases the rate of bacterial-induced human macrophage cell death
1 The Center for Microbial Interface Biology, Division of Infectious Diseases, Department of Medicine, The Ohio State University, Columbus, OH 43210, US
2 Departments of Medicine and Microbiology, University of Iowa, Iowa City, IA 52240, US
3 School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Address correspondence to: Larry S. Schlesinger, Center for Microbial Interface Biology, Division of Infectious Diseases, Department of Medicine, The Ohio State University, 460 W. 12th Ave., Biomedical Research Tower, Room 1002, Columbus, OH 43210, US. Phone: +1 (614) 292-8789. Fax: +1 (614) 292-9616. Email: larry.schlesinger{at}osumc.edu
Received on February 4, 2009; accepted on March 17, 2009
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 
-[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 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 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.
Key words: Mycobacterium tuberculosis / mannosyltransferase / lipoarabinomannan / phosphatidyl-myo-inositol mannoside / macrophage death
* Both authors contributed equally in the performance of this work.
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