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1 Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia, Canada V5Z 3J5
2 Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
3 Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
Correspondence
Yossef Av-Gay
yossi{at}interchange.ubc.ca
The mshB gene encoding N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-
-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. Disruption of mshB in Mycobacterium smegmatis resulted in decreased production of mycothiol (5–10 % of the parent strain mc2155) but did not abolish mycothiol synthesis completely. Complementation of the MshB- mutants with the mshB gene resulted in increased mycothiol production towards the exponential and stationary phases of the bacterial growth cycle. These results suggest that another enzyme is capable of mycothiol biosynthesis by providing N-acetylglucosaminylinositol deacetylation activity in the absence of MshB. One of the candidate enzymes capable of carrying out such reactions is the MshB orthologue mycothiol amide hydrolase, MCA. However, epichromosomal expression of mca in the MshB- mutants did not restore mycothiol levels to the level of the parent strain. Unlike other mutants, which have little or no detectable levels of mycothiol, the MshB- mutant did not exhibit increased resistance to isoniazid. However, the MshB- mutant was resistant to ethionamide. Phenotypic analysis of other mutants lacking mycothiol revealed that MshA- mutants also exhibit ethionamide resistance but that a MshC-mutant was sensitive to ethionamide, suggesting that mycothiol or its early intermediates influence ethionamide activation.
-D-glucopyranoside; GlcN-Ins, 1-D-myo-inosityl-2-deoxy--D-glucopyranoside; LB, Lennox L broth; mBBr, monobromobimane; MCA, mycothiol amide hydrolase; OADC, oleic acid, albumin, dextrose [glucose], catalase supplement; TSB, trypticase soy brothThis article has been cited by other articles:
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  K. P. Bzymek, G. L. Newton, P. Ta, and R. C. Fahey Mycothiol Import by Mycobacterium smegmatis and Function as a Resource for Metabolic Precursors and Energy Production J. Bacteriol., October 1, 2007; 189(19): 6796 - 6805. [Abstract] [Full Text] [PDF]
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 G. L. Newton, P. Ta, K. P. Bzymek, and R. C. Fahey Biochemistry of the Initial Steps of Mycothiol Biosynthesis J. Biol. Chem., November 10, 2006; 281(45): 33910 - 33920. [Abstract] [Full Text] [PDF]
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N. A. Buchmeier, G. L. Newton, and R. C. Fahey A Mycothiol Synthase Mutant of Mycobacterium tuberculosis Has an Altered Thiol-Disulfide Content and Limited Tolerance to Stress. J. Bacteriol., September 1, 2006; 188(17): 6245 - 6252. [Abstract] [Full Text] [PDF]
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S. Kovacevic, D. Anderson, Y. S. Morita, J. Patterson, R. Haites, B. N. I. McMillan, R. Coppel, M. J. McConville, and H. Billman-Jacobe Identification of a Novel Protein with a Role in Lipoarabinomannan Biosynthesis in Mycobacteria J. Biol. Chem., April 7, 2006; 281(14): 9011 - 9017. [Abstract] [Full Text] [PDF]
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 N. Pick, M. Rawat, D. Arad, J. Lan, J. Fan, A. S. Kende, and Y. Av-Gay In vitro properties of antimicrobial bromotyrosine alkaloids. J. Med. Microbiol., April 1, 2006; 55(Pt 4): 407 - 415. [Abstract] [Full Text] [PDF]
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M. Rawat, M. Uppal, G. Newton, M. Steffek, R. C. Fahey, and Y. Av-Gay Targeted Mutagenesis of the Mycobacterium smegmatis mca Gene, Encoding a Mycothiol-Dependent Detoxification Protein J. Bacteriol., September 15, 2004; 186(18): 6050 - 6058. [Abstract] [Full Text] [PDF]
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