Regulation of the periplasmic stress responses in E. coli and P. aeruginosa

Abstract

The ability to adapt to changing environments is essential to survival. Bacteria have developed sophisticated means by which they sense and respond to stresses imposed by changes in the environment. I have undertaken the study of elements of the TE stress response pathway in the bacterium Escherichia coli and the orthologous pathway in the bacterium Pseudomonas aeruginosa. These pathways sense stress in the periplasm and relay the signal into the cytoplasm by a series of proteolytic cleavages of a transmembrane regulatory protein. In E. coli, I have undertaken the study of the regulation of the cleavage of transmembrane regulator RseA by the first protease, DegS. I discovered that RseB, an RseA-binding protein, inhibits cleavage of RseA by DegS. The interaction between RseA and RseB is strong and specific, and the inhibition of cleavage is independent of the autoinhibition of DegS by its PDZ domain. In P. aeruginosa, I have demonstrated that AlgW, the homolog of DegS, cleaves the transmembrane regulator MucA. I have shown similar inhibitory effects of the ortholog of RseB on the ortholog of RseA. Interestingly, the PDZ domain of AlgW appears to function differently from that of DegS. In addition, I observed that a regulatory loop in the AlgW protease plays an inhibitory role in the binding of substrate.