Requirements and strategies for winning the battle against antibiotic resistance by antisense technology

Kotil, Seyfullah Enes

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https://hdl.handle.net/2142/95600 Copy

Description

Title

Requirements and strategies for winning the battle against antibiotic resistance by antisense technology

Author(s)

Kotil, Seyfullah Enes

Issue Date

2016-12-02

Director of Research (if dissertation) or Advisor (if thesis)

Jakobsson, Eric

Doctoral Committee Chair(s)

Jakobsson, Eric

Committee Member(s)

• Blanke, Steven
• Sinha, Saurabh
• Kuhlman, Thomas
• DeVille, Lee

Department of Study

School of Molecular & Cell Bio

Discipline

Biophysics & Computnl Biology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Antibiotic resistance
• Evolution of antibiotic resistance
• designing antisense molecules
• off-target
• sustainable therapy
• reversing antibiotic resistance
• blocking antibiotic resistance
• guiding antibiotic resistance
• directed evolution

Abstract

In chapter 1 we have investigated the different requirements and conditions for efficiency and specificity of antisense molecules. For specific therapy, an antibacterial RNA must be able to distinguish between its designed targets and its off-targets. This distinction is reflected in the binding energy calculations. The major component of efficiency and specificity is uncovered to be the nature of the off-targets. We have made a new thermodynamic based model to explain in-vivo antisense binding. We have shown that it fits previously unexplained experimental data perfectly. The second chapter deals with how to preserve effective therapy in evolving population. The effectiveness of redesigning on resistance is conditioned on rescuing the hybridization affinity. The hybridization affinity can be rescued if the mutations for acquiring resistance were on the target sequence. However there can be mutations elsewhere in the genome that would confer resistance. We have investigated possible therapy strategies to direct the bacteria to take mutations that are on the target. Having multiple entry mechanisms for RNA therapy seems to be the key to directing bacteria towards a sustainable therapy. Third chapter deals with the following: Using antisense therapy to block progression of antibiotic resistance for trimethoprim. Converge bacteria to desired mutations. Using antisense molecules to induce loss of trimethoprim resistance mutations

Graduation Semester

2016-12

Type of Resource

text

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http://hdl.handle.net/2142/95600

Copyright and License Information

Copyright 2016, Seyfullah Enes Kotil

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