Biology Bldg. 425
van Kessel Lab website
- Bacterial cell-cell communication (quorum sensing)
- Gene regulation
- Bacterial development
- Microbial genetics and biochemistry
The van Kessel lab studies how bacteria switch from acting as individuals to behaving as groups. Bacteria use the cell-cell communication process called quorum sensing to sense and respond to changes in the number and type of cells in the surrounding community. Through quorum sensing, bacterial cells synchronously alter gene expression to change modes of behavior.
We are interested in the genetic and molecular mechanisms that coordinate this developmental switch. The focus of our research is on LuxR, the master regulator of quorum-sensing gene expression in vibrios. Vibrios are γ-proteobacteria that live in marine environments and are pathogens of humans, fish, and shellfish. In these bacteria, LuxR functions as a transcriptional activator and repressor of more than 600 genes in a complex pattern to elicit a group behavior response.
Vibrio harveyi, our model bacterium, uses quorum sensing to regulate production of bioluminescence, the beautiful blue glowing color of the colonies pictured on this website. Many of the processes controlled by quorum sensing influence cell growth and development, including pathogenesis, symbiosis, and responses to nutrient stress. Our research aims to gain a mechanistic understanding of how cell-cell communication directly impacts bacteria in their environmental niches.
Quorum sensing in Vibrio harveyi
Quorum sensing relies on extracellular signaling molecules called autoinducers (AIs). As a population of quorum-sensing bacteria grows, the extracellular concentration of AIs increases. When a signal threshold is reached, the group responds with a population-wide alteration in gene expression. Our lab studies quorum sensing in the model organism Vibrio harveyi. V. harveyi makes and responds to three AIs that enable three modes of communication: intraspecies, intragenus, and interspecies. At low cell density (LCD), the extracellular AI concentration is low. The three membrane-bound sensors begin a phosphotransfer cascade that represses translation of the master quorum-sensing transcription factor LuxR and stimulates translation of AphA, the LCD master transcription factor. At LCD, AphA levels are high and LuxR levels are low. As cells grow and divide, the extracellular concentration of AIs increases proportionally in the surrounding environment. At high cell density (HCD), the concentration of AIs is also high. AI binding to the membrane-bound receptors reverses the phosphorylation cascade, which produces LuxR protein and terminates AphA translation. Thus, high levels of LuxR are made at HCD, while AphA is only present at LCD. LuxR activates 625 genes at HCD, many of which are required for physiologically important group behaviors.
Mechanisms of LuxR transcriptional regulation of quorum-sensing genes
V. harveyi LuxR is the founding member of the group of transcription factors that control quorum sensing in all vibrios. LuxR shares high amino acid identity with other LuxR proteins: 71% with HapR (Vibrio cholerae), 96% with OpaR (Vibrio parahaemolyticus), and 93% with SmcR (Vibrio vulnificus). LuxR is a unique member of the TetR family of transcription factors that both activates and represses a regulon of >600 genes through binding to a degenerate consensus DNA binding motif. There is currently a gap in existing knowledge of TetR regulatory mechanisms because LuxR is the only known TetR protein that activates transcription. We are using a combination of structural biology, biochemistry, genetics, and chemistry to determine how LuxR functions as an activator and a repressor of quorum-sensing genes.
Quorum-sensing regulation of group behaviors in vibrios
Among the >600 genes controlled by quorum sensing through LuxR are genes required for type III secretion, type VI secretion, motility, and osmotic stress regulation. We are interested in the patterns of gene expression that control these important physiological outputs. LuxR, AphA, and the Qrrs are the central regulators of these expression patterns, though other downstream transcription factors also play important roles. Using bacterial genetics, bioinformatics, and biochemistry, we are examining the hierarchy of gene regulation that contributes to expression of key developmental and physiological pathways in vibrios.
Genomics and Bioinformatics
Microbial Cell Biology and Environmental Responses
Microbial Interactions and Pathogenesis