Interactions underlying resilient bacterial communities and successful colonization of host niches

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

Bacteria naturally inhabit different niches in the human host, such as the gut, and can opportunistically colonize sterile niches, such as tumors. Bacterial success in these complex environments depends on multiple factors that include the niche conditions and interactions with neighboring microorganisms. Our research leverages on genetically tractable model systems to study bacterial communities in vitro and bacterial colonization of host niches in vivo. We apply an interdisciplinary approach that combines functional genomics, computational analysis, and mathematical modeling to study these complex and dynamic systems. The first focus area is on investigating the factors that underly the complex spatial and temporal patterns observed in natural bacterial communities. Building on our previous work, we will use genetically engineered bacteria to implement mutualistic and competitive interactions and test how specific community properties emerge and change as a function of interaction parameters. Specifically, we will investigate how parameters of the community members dictate the spatial patterns that emerge when multi-member colonies form. We will also investigate the temporal patterns that form in cross-feeding communities and their capacity to support multi-member communities that are not exclusively co-dependent (often observed in nature). Addressing these questions in genetically tractable bacterial consortia will allow to disentangle some of the hidden rules that sustain complex microbial communities found in natural niches, such as the human gut. Resolving these rules will allow genetically engineering robust consortia for biotechnological and biomedical applications. Our second focus area is on bacterial colonization and adaptation to different host niches. Specifically, we will investigate bacterial colonization in an existing microbiome niche – the intestinal tract, and bacterial takeover of a sterile niche – solid cancer tumors. Work will use collections of thousands of bacterial mutants as well as collections of thousands equally fit wild-type E. coli clones tagged with DNA barcodes. Mutant collections allow inferring the bacterial pathways and processes needed for successful colonization while collections of equally fit clones allow inferring the dynamics of a bacterial population experiencing uniform selection. Measurements of bacterial load and clone (barcode) diversity in different colonization stages will be used to determine population bottlenecks, growth and death rates, and for evaluating alternative mathematical models of niche takeover. Our work will deepen the understanding of selection forces operating in the intestinal niche and will uncover, for the first time, the selection forces and population dynamics that govern bacterial infection of solid cancer tumors, an area in the field of tumor-microbiome research that is highly underexplored.