An Investigation Into The Role Of Transfer RNA In Pathogenicity And Drug Resistance In The Human Fungal Pathogen, Aspergillus fumigatus

  • Lauren Dineen

Student thesis: Phd


Aspergillus fumigatus is a filamentous saprophyte that can cause life-threatening infection in immunocompromised individuals. The treatment options are limited and resistance to existing antifungals is on the rise. A. fumigatus has adapted ways to overcome host immunity and cause infection. This requires complex stress response mechanisms, some of which have been studied in detail. Similarly, several mechanisms of drug resistance have been characterised. The role of transcriptional adaptation in stress response and drug resistance has been heavily studied in A. fumigatus. However, novel avenues of research are needed. This thesis focuses on the role of translational adaptation to stress response and drug resistance in A. fumigatus. Transfer RNA (tRNA) are integral to translation, more recently however a multifaceted role for tRNA in stress response has been elucidated. We hypothesised that tRNA may be required for stress response and drug resistance in A. fumigatus. We characterised the tRNA-ome in detail in this important human pathogen and generated a molecularly barcoded tRNA null mutant library. We then employ a competitive fitness screening method to functionally analyse the role of tRNA in stress response and drug resistance. We show that although A. fumigatus displays robustness to tRNA deletion, certain tRNAs contribute to cellular fitness in a condition dependant manner. Finally, we draw focus on a valine tRNA that is involved in azole sensitivity and iron starvation stress response.
Date of Award1 Aug 2023
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorDaniela Delneri (Supervisor), Michael Bromley (Supervisor) & Paul Bowyer (Supervisor)


  • Fungal disease
  • transfer RNA
  • Fungi
  • Aspergillus fumigatus
  • Fitness profiling

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