Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

22-POS Board 22 LIPID REMODELLING AND ACIDIC PH COOPERATIVELY DRIVE MYCOBACTERIAL SURVIVAL VIA MITOCHONDRIAL STRESS AND MEMBRANE ADAPTATION Saitali Laha Roy ; Shobhna Kapoor Indian Institute of Technology Bombay, Chemistry, Mumbai, India Mycobacterial persistence within host cells is governed by its ability to remodel cell envelope lipids and adapt to intracellular stress conditions such as acidic pH. In this study, we investigate how metabolically labelled trehalose dimycolate (TDM) and pH-dependent membrane dynamics collectively regulate host–pathogen interactions and bacterial survival. Using Mycobacterium smegmatis labelled with trehalose-based lipid probes, we observed a significant increase in intracellular bacterial burden in A549 cells at later stages of infection, despite potentially reduced initial uptake. This enhanced survival is associated with modulation of host immune responses, where ELISA analysis revealed a balanced induction of pro-inflammatory (IL-8) and anti inflammatory (IL-10) cytokines, suggesting immune evasion and reduced bacterial clearance. At the cellular level, TDM-labelled infection induced pronounced mitochondrial remodelling, characterized by increased fragmentation and sphericity. This was accompanied by elevated reactive oxygen species (ROS) production, indicating mitochondrial stress. Interestingly, mitochondrial membrane potential was relatively preserved compared to unlabelled infection, suggesting a controlled stress response that supports host cell survival while permitting bacterial persistence. In parallel, exposure to acidic conditions mimicking lysosomal pH (4.5) led to significant alterations in mycobacterial membrane organization. Fluorescence-based measurements indicated increased membrane fluidity and lipid reorganization under acidic stress, potentially enhancing membrane adaptability. Such changes promoting extracellular vesicle release, facilitating the spread of bacterial components and contributing to infection of bystander cells. Collectively, our findings reveal a synergistic mechanism wherein TDM mediated host modulation and pH-driven membrane adaptation converge to enhance mycobacterial survival, stress tolerance, and intracellular propagation, providing new insights into host–pathogen dynamics and potential therapeutic targets.

63