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The Cpx envelope stress response and trkA mutation
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- Author / Creator
- Bannerman-Akwei, Laude
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The fitness and survival of bacteria depends on their ability to adapt and survive in different ecological niches during its life cycle. Bacteria must therefore be able to sense the different changes in the environment during the transition between different ecological niches to enhance survival. The Cpx two component signal transduction system (TCS) is one of the widely known signal transduction systems employed by bacteria to sense and respond to envelope stress to maintain the integrity of the envelope. The Cpx system consists of an inner membrane sensor kinase, CpxA and its periplasmic inhibitor CpxP as well as a cytoplasmic response regulator, CpxR. In the presence of envelope stress, CpxA is relieved of CpxP inhibition, autophosphorylates and subsequently phosphorylates CpxR. Phosphorylated CpxR acts as a transcription factor and regulates the expression of several genes to mediate envelope stress caused by mis-folded proteins in the periplasm. The Cpx response is also up regulated by mutations that affect transport, particularly by antibiotic efflux pumps. Further, part of the Cpx-mediated response involves alterations of the regulation of a variety of transporter genes. However, the connections between transport and the Cpx response are not fully understood. In this study, we investigated the connection between the Cpx response and the Trk system (A transport system that imports potassium into cell). We confirm that induction of the Cpx pathway is specific to mutation of trkA and CpxR dependent but did not require CpxA. The Cpx response is known to be inhibited at acidic pH. We show that when trkA is mutated, this inhibition no longer occurs. In addition, excess potassium does not play a role in the activation of the Cpx system. Furthermore, we demonstrate that mutation of trkA does not elevate Cpx activity by inhibiting CpxA phosphatase activity or by altering the levels of acetyl phosphate. Also, mutation of trkA alters the levels and/or ratio of NAD+/NADH in the cell. Finally, we show that induction of the Cpx system diminishes respiration in the trkA mutant. Our work demonstrates that the Cpx pathway uses novel mechanism to sense and respond to changing cellular physiology associated with transport and metabolism.
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- Subjects / Keywords
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- Graduation date
- Spring 2018
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.