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Microbiology 146 (2000), 199-208
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Microbiology (2000), 146, 199-208.
© 2000 Society for General Microbiology

Genetics and Molecular Biology

Three pathways for trehalose biosynthesis in mycobacteria

Koen A. L. De Smetb,1, Anthony Westonc,2, Ivor N. Brown1, Douglas B. Young1 and Brian D. Robertson1

Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, St Mary’s Campus, Norfolk Place, London W2 1PG, UK1
Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, UK2

Author for correspondence: Brian D. Robertson. Tel: +44 20 7594 3965. Fax: +44 20 7262 6299. e-mail: b.robertson{at}ic.ac.uk

Trehalose is present as a free disaccharide in the cytoplasm of mycobacteria and as a component of cell-wall glycolipids implicated in tissue damage associated with mycobacterial infection. To obtain an overview of trehalose metabolism, we analysed data from the Mycobacterium tuberculosis genome project and identified ORFs with homology to genes encoding enzymes from three trehalose biosynthesis pathways previously characterized in other bacteria. Functional assays using mycobacterial extracts and recombinant enzymes derived from these ORFs demonstrated that mycobacteria can produce trehalose from glucose 6-phosphate and UDP-glucose (the OtsA–OtsB pathway) from glycogen-like {alpha}(1->4)-linked glucose polymers (the TreY–TreZ pathway) and from maltose (the TreS pathway). Each of the pathways was found to be active in both rapid-growing Mycobacterium smegmatis and slow-growing Mycobacterium bovis BCG. The presence of a disrupted treZ gene in Mycobacterium leprae suggests that this pathway is not functional in this organism. The presence of multiple biosynthetic pathways indicates that trehalose plays an important role in mycobacterial physiology.

Keywords: genome, mycobacteria, osmotic stress, trehalose, tuberculosis

Abbreviations: MOT, maltooligosyltrehalose

b Present address: Innogenetics NV, Industriepark Zwijnaarde, 9052 Ghent, Belgium.

c Present address: Cytocell Ltd., Somerville Court, Banbury Business Park, Adderbury, Oxford OX17 3SN.




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