Inter-kingdom signaling: In contradiction of the traditional view of bacteria being non-communicating primitive organisms, recent advances in bacteriology prove that bacteria do possess cell-cell chemo-sensing mechanisms. Bacterial cells communicate with each other using small molecules, such as Acyl-Homoserine Lactones (AHL) and oligopeptides to coordinate population behaviours such as biofilm formation and swarming motility. Such cell-cell communication is termed as quorum sensing, and is central to the pathogenicity of many bacterial pathogens. Bacteria also use AHLs and other small molecules to interact with mammalian host cells, and modulate inflammatory and immune responses, a process termed as inter-kingdom signaling. Such chemosensation between bacterial cells with the host is an exciting new area of research for understanding bacterial pathogenesis and the pathogen-host interactions.
Collaborative research within MCSB currently investigates the interactions between bacterial AHL signal molecules and human airway cells. The possibility that T2Rs serve as the mediators of AHLs on lung epithelial cells is being explored. T2R activation by bacterial signals is monitored using real-time cellular analysis techniques. Bacterial type III secretion system which alters host cell behaviours by injecting bacterial toxins directly to mammalian cells is also being investigated to delineate the signal transduction and pathophysiological interactions between pathogenic bacteria and the host. Both new knowledge and basis for new technology can be anticipated from this research.
Efflux pumps, antibiotic resistance and chemosensation: One of the most important mechanism of intrinsic antibiotic resistance in Gram-negative bacterial species like Pseudomonas aeruginosa is through the activity of energy-dependent efflux pumps, particularly those belonging to the Resistance-Nodulation-Division (RND) pumps. One fascinating characteristic of RND pumps is their broad-substrate profile. Apart from pumping out structurally unrelated antibiotic molecules, they are also believed to efflux molecules involved in quorum sensing or their precursors.
Our collaborative work with other members of the MCSB group involves studying the role of RND efflux pumps in chemosensation between pathogens and the host and thereby understanding the role of these pumps in interplay between virulence and antibiotic resistance.