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Journal of Bacteriology, June 2008, p. 4335-4341, Vol. 190, No. 12
0021-9193/08/$08.00+0     doi:10.1128/JB.01825-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Critical Role of embC in Mycobacterium tuberculosis

Centre for Infectious Disease, Barts and The London, Queen Mary's School of Medicine and Dentistry, London E1 2AT, United Kingdom,¹ Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523²

Received 19 November 2007/ Accepted 8 April 2008

Arabinan polymers are major components of the cell wall in Mycobacterium tuberculosis and are involved in maintaining its structure, as well as playing a role in host-pathogen interactions. In particular, lipoarabinomannan (LAM) has multiple immunomodulatory effects. In the nonpathogenic species Mycobacterium smegmatis, EmbC has been identified as a key arabinosyltransferase involved in the incorporation of arabinose into LAM, and an embC mutant is viable but lacks LAM. In contrast, we demonstrate here that in M. tuberculosis, embC is an essential gene under normal growth conditions, suggesting a more crucial role for LAM in the pathogenic mycobacteria. M. tuberculosis EmbC has an activity similar to that of M. smegmatis EmbC, since we were able to complement an embC mutant of M. smegmatis with embC_Mtb, confirming that it encodes a functional arabinosyltransferase. In addition, we observed that the size of LAM produced in M. smegmatis was dependent on the level of expression of embC_Mtb. Northern analysis revealed that embC is expressed as part of a polycistronic message encompassing embC and three upstream genes. The promoter region for this transcript was identified and found to be up-regulated in stationary phase but down-regulated during hypoxia-induced nonreplicating persistence. In conclusion, we have identified one of the key genes involved in LAM biosynthesis in M. tuberculosis and confirmed its essential role in this species.

Published ahead of print on 18 April 2008.