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Abstract:
The human gut microbiome consists of trillions of organisms from all three domains of life. This complex and interconnected system is driven by the biological interactions between its constituents (host-microbe, microbe- microbe) and plays a major role in human health and development. However, we know very little about the specific mechanisms driving these interactions. The application of microbial genetics to the gut microbiome represents a powerful opportunity to tease out the functional basis for community dynamics, yet the majority of gut-associated microbes are genetically intractable. This is primarily due to an incompatibility between traditional genetic tools (developed for model organisms like E. coli) and the phylogenetically diverse non-model organisms associated with the human gut. In response, we have developed a conjugation donor optimized for compatibility with diverse gut organisms and the anaerobic conditions in which they are cultured. The donor incorporates strategies for microbial defence system inactivation, a kill-switch for counter-selection following DNA transfer, and a conjugation system that can be "primed" for diverse recipients. This represents the first microbiome-specific genetic tool in this emerging era of microbiome genetics and engineering and will potentially enable a deeper and more mechanistic understanding of human gut microbiome interactions.
