The Critical Role ofembCinMycobacterium tuberculosis

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Abstract
Arabinan polymers are major components of the cell wall inMycobacterium tuberculosisand 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 speciesMycobacterium smegmatis, EmbC has been identified as a key arabinosyltransferase involved in the incorporation of arabinose into LAM, and anembCmutant is viable but lacks LAM. In contrast, we demonstrate here that inM. tuberculosis,embCis an essential gene under normal growth conditions, suggesting a more crucial role for LAM in the pathogenic mycobacteria.M. tuberculosisEmbC has an activity similar to that ofM. smegmatisEmbC, since we were able to complement anembCmutant ofM. smegmatiswithembCMtb, confirming that it encodes a functional arabinosyltransferase. In addition, we observed that the size of LAM produced inM. smegmatiswas dependent on the level of expression ofembCMtb. Northern analysis revealed thatembCis expressed as part of a polycistronic message encompassingembCand 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 inM. tuberculosisand confirmed its essential role in this species.