| Summary: | <p>Abstract</p> <p>Background</p> <p>Proteins that are involved in regulation of cell division and cell cycle progression remain undefined in <it>Mycobacterium tuberculosis</it>. In addition, there is a growing appreciation that regulation of cell replication at the point of division is important in establishing a non-replicating persistent state. Accordingly, the objective of this study was to use a systematic approach consisting of consensus-modeling bioinformatics, ultrastructural analysis, and transcriptional mapping to identify septum regulatory proteins that participate in adaptive metabolic responses in <it>M. tuberculosis</it>.</p> <p>Results</p> <p>Septum site determining protein (Ssd), encoded by <it>rv3660c </it>was discovered to be an ortholog of septum site regulating proteins in actinobacteria by bioinformatics analysis. Increased expression of <it>ssd </it>in <it>M. smegmatis </it>and <it>M. tuberculosis </it>inhibited septum formation resulting in elongated cells devoid of septa. Transcriptional mapping in <it>M. tuberculosis </it>showed that increased <it>ssd </it>expression elicited a unique response including the dormancy regulon and alternative sigma factors that are thought to play a role in adaptive metabolism. Disruption of <it>rv3660c </it>by transposon insertion negated the unique transcriptional response and led to a reduced bacterial length.</p> <p>Conclusions</p> <p>This study establishes the first connection between a septum regulatory protein and induction of alternative metabolism consisting of alternative sigma factors and the dormancy regulon that is associated with establishing a non-replicating persistent intracellular lifestyle. The identification of a regulatory component involved in cell cycle regulation linked to the dormancy response, whether directly or indirectly, provides a foundation for additional studies and furthers our understanding of the complex mechanisms involved in establishing a non-replicating state and resumption of growth.</p>
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