Host-bacterial coevolution and the search for new drug targets

Understanding the coevolution between humans and our microbial symbionts and pathogens requires complementary approaches, ranging from community analysis to in-depth analysis of individual genomes. Here we review the evidence for coevolution between symbionts and their hosts, the role of horizontal gene transfer in coevolution, and genomic and metagenomic approaches to identify drug targets. Recent studies have shown that our symbiotic microbes confer many metabolic capabilities that our mammalian genomes lack, and that targeting mechanisms of horizontal gene transfer is a promising new direction for drug discovery. Gnotobiotic (‘germ-free’) mice are an especially exciting new tool for unraveling the function of microbes, whether individually or in the context of complex communities.