The symbiotic relationship between the nitrogen-fixing Sinorhizobium meliloti and its legume host (Medicago sativa) is the result of an intricate signaling network between the host and the symbiont. We have shown that quorum sensing, a process that involves the population density-dependent regulation of gene expression, plays an integral part of this complex association. This process involves the release and detection of small extra-cellular signal molecules termed autoinducers. The best characterized of these autoinducers are acylated homoserine lactones (AHLs), mostly found in gram-negative organisms. The overall goal of this research is to determine the role that quorum-sensing plays in the well-characterized relationship between S. meliloti and its host. As a result of our recent work, this symbiotic association is rapidly becoming a paradigm for the study of quorum sensing. S. meliloti possesses a complex series of linked quorum-sensing systems. We have characterized three of those systems (Mel, Sin and Tra) and established that they play a part in nodulation, exopolysaccharide production, nitrogen fixation and conjugal plasmid transfer. The Sin system produces the longest AHLs detected to date. Our work has determined that one of these long-chain AHLs plays a key role in regulating the production of the syrnbiotically important exopolysaccharide II. In addition, the Sin quorum-sensing system affects the timing and number of nodules it induces on its plant host.
The first aim of this proposal is to determine how the multiple quorum-sensing systems of S. meliloti are regulated and coordinated. This will provide insights into a regulatory aspect of quorum sensing that is impossible to study in the presently employed model systems. Second, we will investigate how the highly hydrophobic AHLs produced by the Sin system are transported across biological membranes. This could help elucidate the mechanisms used by the transmembrane pumps that confer resistance to cytotoxic drugs and potentially arm us in the struggle to fight multidrug resistance by enabling the rational design of inhibitors of these pumps. Third, this project seeks to identify, through microarray analysis, the genes controlled by the Sin and Mel quorum sensing systems and determine their function in the S. meliloti/alfalfa symbiosis. This study will provide a better understanding of the symbiotic/pathogenic relationships between prokaryotes and their eukaryotic hosts and might provide tools for the control and manipulation of such relationships.
Showing the most recent 10 out of 11 publications
