Bacterial organisms inhabit diverse eukaryotes where their presence can have consequences for important traits of their host such as host development, nutrition or behavior. Eukaryotes thus constitute an ecological niche for microbial communities that utilize the resources of their habitat host. The microbiota biodiversity and composition over the host life cycle is determined by a combination of three main factors: 1) the host-habitat properties, including abiotic and biotic factors (i.e., selection on the microbiota), 2) species interactions (e.g., colonization dynamics), and 3) genetic variation (i.e., microbial evolution).
In this new tandem project B4 of the CRC, we aim to characterize microbial traits that play a role in species interactions and microbial adaptation within the host-habitat. Our research will include several hosts that are studied within the CRC including sponge (B1), jellies (B2), C. elegans (A4), mammals (A2) and wheat (A3). The PIs in this project have complementary expertise in bacterial genetics, bacterial genome evolution and comparative genomics. Specifically, we will combine comparative genomics with experimental approaches to (1) systematically identify bacterial traits unique to host-associated bacteria and (2) study mechanisms of colonization resistance in the context of competitive exclusion of pathogens.
In subproject B4.1 (PI Dagan), we will test the hypothesis that adaptation to the host habitat entails evolution of lifestyle traits that are found among host-associated bacteria and absent in their free-living counterparts. An emphasis will be on genes that encode for mechanisms of currency, currency exchange and communication. Available genome sequences will be analyzed in a phylogenomics approach to identify genes unique to host-associated bacteria in contrast to free-living ones.
In subproject B4.2 (PI Unterweger) we will study mechanisms of species interaction, with a focus on bacterial toxins and follow-up on the distribution of bacterial toxins among host associated and free-living bacteria. Individual toxins such as Bte2 secreted by a type VI secretion system (T6SS) are known to benefit their host by killing pathogens and mediate colonization resistance. How bacteria use their T6SS to kill pathogens is less well understood. We will perform experiments to determine the molecular mechanism of T6SS-mediated colonization resistance of symbiotic Bacteroides in mammals. The results of our mechanistic study on Bacteroides will be interpreted in the context of the results of the systematic analysis of symbiotic traits across hosts.
This project is one of the first to systematically dissect the mechanisms by which bacteria colonize and inhabit their host and assess the importance of T6SS-mediated functions for host-microbiota interactions. The project will thus yield novel insights into the genetic determinants of communication and recognition within host-associated microbiota.