Research Projects

Bacteria have the extraordinary ability withstand and sense their environment through mechanosensory receptors like PilY1, PhoQ/PhoP, and Ysc enabling them to adapt to diverse cues and perform critical cellular functions. Among these, Pseudomonas aeruginosa (PA) is a nosocomial pathogen notorious for its multidrug resistance (MDR), presenting significant challenges in treating infections. Beyond healthcare, PA also known to disrupt industrial pipelines by forming robust biofilms. Current treatment approaches, particularly antibiotics, have only exacerbated the issue by facilitating MDR strains. This proposal focuses on PA rheosensation ability to sense and respond to fluid flow—to understand its role in motility, growth, metabolism, and virulence activation. The research is structured around three key objectives. Obj 1 explores how PA responds to varying flow conditions in microfluidic devices simulating fluid flow in patients. Flow parameters like velocity, pulsation frequency, and fluid composition will be regulated to analyze bacterial motility, twitching patterns, and biofilm formation. Obj 2 examines the role of rheosensation in growth and metabolism by measuring metabolic indicators, including ATP production and NADH/NAD+ ratios, and by monitoring biofilm-related extracellular polymeric substance (EPS) formation under controlled flow conditions. Obj 3 investigates the connection between rheosensation and virulence development. By analyzing virulence factors such as pyocyanin and pyoverdine, and validating the role of the cGMP signaling pathway. This study will determine how flow conditions would enhance virulence using infection models like amoebae, waxworms, and Drosophila. The overarching hypothesis is that rheosensation regulates key physiological and pathogenic responses in PA. The research aims to identify molecular mechanisms linking fluid dynamics to bacterial behaviour, thereby offering a novel antimicrobial strategy instead of conventional chemical treatment. Experiments will utilize custom-built microfluidic devices, and a centralized facility will be established for device fabrication and shared research resources, encouraging collaboration across disciplines. This study has far-reaching implications in the clinical and industrial settings. It will advance fundamental knowledge of mechanosensory pathways and their impact on bacterial motility, biofilm formation, and virulence. The findings are expected to inform the development of innovative therapies targeting rheosensory mechanisms, reducing MDR infections in clinical settings and biofilm-related challenges in industrial systems. By bridging gaps in understanding and fostering interdisciplinary collaboration, this project has the potential to revolutionize approaches to bacterial infection control and biofilm mitigation.