The Social Network of Microbes: New Methods to Unravel Microbial Community Dynamics
Abstract
Microorganisms engage in complex interactions with other organisms and their environment. Recent studies have demonstrated that these interactions are reaching beyond the simple exchange of electron donors. Complex intertwined exchanges of amino acids, vitamins, and other cofactors lay the foundation microbial communities are build on. These interactions are not static but are highly dynamic in nature and change over time. Same as our own network of social interaction changes and evolves over time, so is the microbial interaction network changing. Nutritional requirements that are hardwired into the genome thus define the network microbes will engage in and contribute significantly to community assembly and maintenance. Currently we lack a deeper understanding about the requirements of microorganisms and how these requirements differ between different strains and different environments. More importantly, we do not know which microbes interact with each other and who would replace the function of a microbe when it is reduced in abundance or removed from a community. Thus we lack the ability to predict keystone species in most microbial communities. There are currently no adequate tools that enable the target reduction or elimination of a specific microorganism from a community and study the effect on the environment. Here we propose to deploy a new method developed by our laboratory that enables targeted depletion or enrichment of specific microorganisms from a community. The method takes advantage of the fact that all bacterial cells contain highly specific glycan binding proteins, i.e. lectins. These lectin-glycan interactions can be as specific as the interaction between antigen-antibody or substrate-enzyme. Gylcans are the most functionally and structurally diverse molecules in biology and are a hallmark of every living cell. We have recently shown that a unique high density and flexible display of glycans enhances multivalent interactions with bacteria and archaea, and thus enables capture of microorganisms based on their glycan binding specificity. We will utilize this array to specifically change the composition of the skin microbiome and follow its dynamics over time in a mouse model. The targeted and gradual removal of members of the microbiome will enable systematical studies of the effect individual species have on community composition and robustness of the microbiome. It will allow delineating outcomes different microorganisms have on community assembly and maintenance and evaluate the effect on the community when the most abundant organism or a keystone species is gradually depleted. Quantitative information generated in this project, e.g. gene expression data, will be used to constrain genome-scale metabolic models for key members of the community. Using a systems biology approach we will gain mechanistic insight into the effect species deletion/enrichment has on community composition. If successful the project will provide answers to fundamental question in microbiome research. We will gain knowledge about how microbial communities are assembled and maintained. Furthermore, we will provide insights into how the community responses to perturbation and what role individual members play in this response. Overall the proposed work will generate a deeper understanding of microbial community composition and function and it will provide the basic knowledge and mechanistic understanding needed for microbiome interventions and design strategies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 11, 2018
- Source ID
- W911NF1810158
Entities
People
- Karsten Zengler
Organizations
- Army Contracting Command
- United States Army
- University of California, San Diego