Research
To colonize the gastrointestinal tract, C. difficile must compete with both the host and members of the gut microbiota for essential nutrient iron. We discovered that C. difficile undergoes an intracellular iron biomineralization process and produces faceted membrane-bound iron phosphate organelles (ferrosomes) to maintain iron balance during transient iron overload. The ferrosome system serves as an iron storage mechanism, is activated in the inflamed gut to combat host-mediated iron sequestration and is important for bacterial colonization and persistence during CDI. However, the molecular basis of ferrosome biogenesis is largely undefined. Ongoing projects in the lab aim to (i) elucidate the underlying mechanisms of ferrosome biogenesis, (ii) define the function of ferrosome iron minerals within the gut community, and (iii) determine the impact of nutrient iron on host-microbe interactions.
Bacterial TCSs are the predominant strategy for stress detection and niche adaptation. TCSs enable cells to sense, respond, and adapt to changes in their environment and regulate a wide variety of processes such as virulence, sporulation, antibiotic resistance, and membrane integrity. TCSs are widespread in bacteria and plants but absent in human and animals, making them potential targets for developing novel antibacterial agents. C. difficile encodes many TCSs (54 histidine kinases and 57 response regulators), reflecting the complex environmental conditions encountered by this pathogen. The Pi lab is interested in understanding (i) how these TCSs are regulated, (ii) what they regulate, and (iii) how this regulation affects cellular physiology and CDI.
Post-transcriptional regulation by RBPs has been well appreciated in eukaryotic gene regulation but remains poorly understood in bacteria, particularly in Gram-positive bacteria such as C. difficile. Post-transcriptional control provides at least two major fitness advantages: (i) it enables a rapid and robust response to alter expression at both gene and protein levels; (ii) it allows cells to fine-tune protein expression by segregating transcription and translation. Ongoing projects aim to uncover the roadmap of RBPs in C. difficile and determine the impact of RBP-mediated regulation on C. difficile pathogenesis.