To Study The Role Of Sigma Factor Sige In The Stringent Response Of Mycobacterium Tuberculosis

Abstract

Bacteria respond to nutrient deprivation by activating the stringent response, a stress signalling system that leads to metabolic remodelling and a reduction in growth rate and energy needs. The model of stringent response in Mycobacterium tuberculosis induced by growth in low phosphate is well-characterized. Prior research suggested that the extracytoplasmic function (ECF) sigma factor SigE plays a crucial role in the activation of the stringent response. Using RNA sequencing, we examine the temporal dynamics of the transcriptional response of a sigE mutant and its wild-type progenitor strain to low phosphate in this study. Both strains exhibited a typical stringent response to reduced phosphate, including the downregulation of genes encoding ribosomal proteins and RNA polymerase- ase. We also observed transcriptional alterations that support the occurrence of an energy imbalance, which was compensated by a decrease in the activity of the electron transport chain, a decrease in the export of protons, and a reorganisation of the central metabolism. The most notable difference between the two strains was the induction of multiple stressrelated genes in the sigE mutant, specifically the genes encoding the ECF sigma factor SigH and the transcriptional regulator WhiB6. Since both proteins respond to redox imbalances, the induction of these proteins suggests that the sigE mutant is unable to maintain redox homeostasis in response to the energetics imbalance induced by low phosphate. In conclusion, our data imply that SigE is not directly involved in initiating stringent response, but rather in protecting the cell from stress resulting from exposure to low levels of phosphate and activation of stringent response. Mycobacterium tuberculosis is capable of entering a quiescent state, which enables it to establish latent infections and develop resistance to antibacterial drugs. Due to the dearth of dependable animal models, the physiology of dormant bacteria and the mechanism(s) by which bacteria enter dormancy during an infection remain unknown. Nonetheless, several in vitro models that replicate the conditions encountered during an infection can reproduce distinct characteristics of dormancy (growth arrest, metabolic deceleration, and drug tolerance). The stringent response is one of them; it is a stress response programme that allows microbes to endure nutrient deprivation. In this study, we provide evidence that the sigma factor SigE is not directly involved in the activation of the stringent response, as was previously hypothesised. However, SigE is
essential for assisting the bacteria in coping with the metabolic stress associated with the adaptation to low phosphate and activation of the stringent response.