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Master's lecture in Bioengineering - Gunes Gurel

When 
Wed, 29/01/2020 - 11:00 to 12:30
Where 

VR-II

Langholt (257)

Further information 
Free admission

Master's student: Gunes Gurel

Title: Adaptive Laboratory Evolution of Escherichia coli MG1655 WT and tolC Knock-out towards Bile Acid and Antibiotic Resistance

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Faculty: Faculty of Industrial Engineering, Mechanical Engineering and Computer Science

Advisor:  Sigurður Brynjólfsson, Professor at the Faculty of Industrial Engineering, Mechanical Engineering and Computer Science

Also in the masters committee: Morten Otto Alexander Sommer and Felipe Gonzalo Tueros Farfan

Examiner: Ólafur Eysteinn Sigurjónsson, Professor at Reykavík University

Abstract

The human microbiome is composed of various commensal and pathogenic microorganisms. Collective research efforts and recent technology have revealed enormous information and contributed to knowledge of the field so far. Studies have described the structure and functional capabilities of the human microbiome in the healthy state and in a variety of disease states. Multi-drug resistance (MDR) poses one of the greatest threats to human health worldwide as bacterial pathogens evolved to withstand antimicrobials and ever-changing environmental conditions more than ever. As the research regarding drug resistance reveals more information over the past decades, one of the most prominent intrinsic self-defense mechanisms, membrane bound tripartite bacterial multi-drug efflux protein acrAB-tolC which removes a wide range of drugs and toxic compounds taken up by commensal gut bacteria is found to greatly be associated with MDR in commensal gut microbiome. The overexpression of these efflux system causes MDR and resistance optimization is driven by mutations in regulatory genes such as marR and acrR which known to increase the expression level of the many other resistance factors including acrAB-tolC protein itself. In this master thesis, the role of tolC efflux channel and in what extend it contributes to MDR in commensal gut bacteria Escherichia coli is assessed in multiple drug evolution settings

using de novo adaptive laboratory evolution method. The findings showed that the absence of fully intact acrAB-tolC and especially tolC channel has a substantial decrease in drug resistance and could not be compensated with any of the most common resistance regulation factors.