Question

Explain in detail how two-component systems detect an environmental signal and mediate a change in transcription in response to the signal. Your answer should include all essential domains and residues.

Answer 1

Two-component regulatory systems (TCRS) plays major role in signal transduction in which mediators of signal transduction that activates bacteria for the detection of physical and/or chemical changes and this signal passes through the cytoplasm to the bacterial nucleoid, the place where modulation of gene expression occurs. TCRS includes membrane-bound sensor kinase and a DNA-binding response regulator. stimuli is generated in response, the sensor kinase is phosphorylated at a conserved histidine residue and then the phosphoryl group is transferred to the conserved aspartate on the response regulator. Phosphorylation as the result of response regulator in which it triggers a conformational change, driving dimerization and high affinity DNA binding. Bacteria differ from eukaryotes in that their signal transduction systems employ histidine phosphorylation rather than tyrosine phosphorylation

Consider an example, gram-negative pathogen Salmonella Typhimurium, which is a frequent cause of bacterial gastroenteritis. After ingestion of contaminated food, Salmonella can travel to the lower intestinal tract where it crosses the intestinal epithelium and is engulfed by resident macrophages. Due to low acidity and low osmolality of the macrophage vacuolar environment ,it acts as an activating signal for various two-component systems, including: EnvZ/OmpR, PhoP/PhoQ, SsrA/SsrB, which enables the pathogen to survive inside host cells. The PhoP/PhoQ TCRS responds to changes in the level of cations like Ca2+ and Mg2+, whereas EnvZ-OmpR, the master regulator, responds to changes in the acidic environment of the macrophage. Both PhoQ/PhoP and EnvZ/OmpR, regulate SsrA/SsrB which eventually regulates SPI-2 expression and secretion of effectors, the SsrA sensor kinase is activated by low pH and phosphorylates the response regulator SsrB. Phosphorylated SsrB de-represses H-NS silencing and activates a set of virulence genes located at the Salmonella Pathogenicity island-2 (SPI-2) region. These genes decode several components of a molecular syringe (Type-III secretion system) that allows the delivery of 30 specialized effector proteins which manipulate the host cellular machinery to ensure the survival and proliferation of intracellular Salmonella.