Bacterial Energetics & Molecular Adaptation
Bacterial Energetics & Molecular Adaptation
Our group investigates the adaptive plasticity of bacterial energy metabolism and its impact on pathophysiology. While our primary aim is to deepen our fundamental understanding of these mechanisms, we also intend to leverage this knowledge to address the antimicrobial resistance crisis. Additionally, we are intrigued by microbial social behavior and its dynamics within the host environment.
The bacterial energetics is elaborate and highly flexible. While the significance of such flexibility is appreciated to ensure robust energy generation, the emergence and optimization of various pathways in the system are poorly understood. It is believed that most components of bioenergetics evolved independently to serve a role different from their modern function.
Evolutionary repurposing and exchange might have resulted in the complex energy metabolism. Interestingly various subunits of energetic system function at their sub-maximal capacity. Using genetic engineering and adaptive laboratory evolution, we explore the rationale for this maximal-optimal disconnect in the system.
Notoriously, bacteria are ubiquitous and capable of surviving in extreme environments. To enable such robust survival strategies, bacterial respiratory and metabolic plasticity is essential. For a pathogenic bacteria, the host offers another such dynamic and often stressful environment. This makes respiro-metabolic plasticity of a pathogen pertinent inside its host.
We aim to understand the important pathophysiological implications of bacterial respiratory plasticity during infection. Using ex vivo infection models, high-throughput omics analysis, and in vitro physiological assays, we attempt to tease out the fundamental details of host-pathogen interactions from an energy metabolism standpoint.
Bacterial cells communicate, cooperate, and compete. Bacteria live a social life and acquire various multicellular forms. Such assemblages allow bacteria to thrive in diverse conditions. Biofilm is one multicellular organization often associated with higher antibiotic tolerance and immune escape within the host, thus contributing to pathogenic success.
The physical and physiological heterogeneity within biofilm requires a spatiotemporal optimization of cellular metabolism. Thus the transition of bacteria from solitary to a social lifestyle requires extensive bioenergetic remodeling. Using synthetic bacterial community set-ups, we explore the mechanistic interplay between energy metabolism and community structuring.