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Background  Proteins that are involved in regulation of cell division and cell cycle progression remain undefined in  Mycobacterium tuberculosis . 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  M. tuberculosis .    Results  Septum site determining protein (Ssd), encoded by  rv3660c  was discovered to be an ortholog of septum site regulating proteins in actinobacteria by bioinformatics analysis. Increased expression of  ssd  in  M. smegmatis  and  M. tuberculosis  inhibited septum formation resulting in elongated cells devoid of septa. Transcriptional mapping in  M. tuberculosis  showed that increased  ssd  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  rv3660c  by transposon insertion negated the unique transcriptional response and led to a reduced bacterial length.    Conclusions  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.

bmc microbiology

Mycobacterium tuberculosis septum site determining protein, Ssd encoded by rv3660c, promotes filamentation and elicits an alternative metabolic and dormancy stress response