These components work together to negatively regulate FtsZ polymerization preventing cell division until DNA replication is complete and the chromosomes have been properly segregated. It is well accepted that
during establishment of a chronic latent infection M. tuberculosis halts cell cycle progression and significantly reduces metabolic activity. One adaptive process that has been associated with limited growth conditions, stress, and pathogenesis is the Dos-response. Under experimental conditions, the Dos learn more regulon is induced in response hypoxia, NO and carbon monoxide [14]. The Dos-response is generally thought to be important for adaptation to alternative growth conditions, thus establishing the ability to endure long periods within the host. The idea that the Dos-response plays a role in pathogenesis is supported Apoptosis inhibitor Selleckchem 3-Methyladenine by studies that have demonstrated that the highly virulent W-Beijing linage of M. tuberculosis exhibits high levels of constitutive expression of the Dos-regulon components [15, 16]. While the DosR two-component regulatory system and primary members of the Dos-regulon are well defined, other components, particularly complimentary regulatory elements that coordinate cell cycle progression and growth in response to alternative growth conditions remain undefined. Because bioinformatics approaches alone have
failed to identify homologs for all cell cycle components, we have previously used inhibition of cell division and transcriptional mapping to identify putative regulatory elements in M. tuberculosis, with particular focus on those that regulate septum formation [6, 7, 17]. The detailed regulatory mechanisms involved in inhibition of septum formation and cell division in M. tuberculosis have not been defined, and will afford an understanding of the mechanisms involved with growth and adaptation to alternative environments signaling the induction of bacteria into a non-replicating state. In order to identify septum regulatory proteins that elicit a transcriptional stress response, a systematic approach consisting of consensus-modeling
bioinformatics, gene dosage and ultrastructural analysis, and expression profiling was employed. As a result, rv3660c was discovered to encode a protein with similarity to Cell press the loosely defined family of septum site determining proteins. Increased expression of rv3360c resulted in filamentous cells, while the disruption of the gene by transposon insertion presented minicell morphology demonstrating an inhibitory role in septum formation. Transcriptional analysis showed that rv3660c expression results in the induction of a unique profile of alternative sigma factors, open reading frames encoding proteins involved in alternative metabolism and the dormancy regulon. Accordingly, this is the first report of a Ssd-like septum regulating protein in M.