Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/137901
Title: EPITRANSCRIPTOMIC REGULATION OF MYCOBACTERIAL STRESS RESPONSE: ROLES OF tRNA MODIFICATIONS IN ANTIBIOTIC RESISTANCE
Authors: CAI WEILING MAGGIE
Keywords: epitranscriptome, mycobacteria, stress response, antibiotics
Issue Date: 15-Aug-2017
Citation: CAI WEILING MAGGIE (2017-08-15). EPITRANSCRIPTOMIC REGULATION OF MYCOBACTERIAL STRESS RESPONSE: ROLES OF tRNA MODIFICATIONS IN ANTIBIOTIC RESISTANCE. ScholarBank@NUS Repository.
Abstract: Tuberculosis remains a global health challenge, largely due to the emergence of persisters refractory to current treatment regime. This persisting population is likely a result of bacteria circumventing and adapting to host stressors to enter a non-replicative, drug-tolerant state. Thus understanding the molecular mechanisms underlying the state of persistence forms a critical basis for therapeutic interventions. This thesis proposed that mycobacteria exploit the epitranscriptome to survive host stressors and attain the consequent phenotypic drug tolerance. Top-down mass spectrometric analysis was performed to interrogate the repertoire of modified ribonucleosides in mycobacterial transfer RNA. We demonstrated stressor-induced dynamic reprogramming of tRNA modifications and identified i6A as a signature modification unique to starvation. Using genetic engineering, we showed that i6A is involved in modulating mycobacterial response to antibiotics and regulating levels of tryptophan. Together, these studies offer novel insights into the epitranscriptomic regulation of mycobacterial stress response.
URI: http://scholarbank.nus.edu.sg/handle/10635/137901
Appears in Collections:Ph.D Theses (Open)

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