アイテム詳細

要旨

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 currently know very little about the specific mechanisms driving these interactions. The application of microbial genetics techniques to the gut microbiome presents a powerful opportunity to tease out the functional basis for community dynamics, yet the majority of gut-associated microbes are genetically intractable and resistant to genetic manipulation. This is primarily due to an incompatibility between traditional genetic tools (that were developed for model organisms like E. coli) and the phylogenetically diverse non-model organisms that are associated with the human gut. In response, we have developed a DNA transfer strategy that has been optimized for compatibility with diverse gut organisms and the anaerobic conditions in which they are cultured. This strategy incorporates 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.