WEHI PhD Completion Seminar hosted by Professor Aaron Jex

Qiao Su

PhD Student – Jex Laboratory, Infection and Global Health division, WEHI

Systems-based approaches to understanding infection, stress responses and drug resistance in parasitic protists

 

Speaker online presentation

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Including Q&A session

Current treatments for giardiasis, a WHO-listed neglected disease caused by the parasitic protist Giardia duodenalis, rely on a limited number of drug classes, including benzimidazoles (BZs; e.g., albendazole, ALB). Nonetheless, increasing resistance and treatment failures threaten their efficacy, posing a significant public health concern. This thesis investigates ALB resistance (ALB-R) mechanisms across human-infective Giardia assemblages. In assemblage A, ALB-R was associated with the E198K ß-tubulin mutation—the first identified protistan BZ-resistance mutation—coupled with cytoskeletal reinforcement, metabolic shifts, and altered protein turnover. Assemblage B, however, developed ALB-R without tubulin mutations, instead adopting a persister-like strategy through genome stabilization, cell cycle arrest, membrane adaptation, translational reallocation, and selective retention of metabolic and cytoskeletal functions. These findings advance the molecular understanding of BZ mode of action and resistance mechanisms, and emphasize the need for assemblage-specific diagnostics and targeted therapeutic strategies to mitigate drug-resistant Giardia infections.

All welcome!