Antibiotic resistance arises as a consequence of complex interactions among genes, mobile elements, and their bacterial hosts, coupled with the intense selection pressures imposed by humans in an attempt to control bacterial growth. Understanding the evolution of resistance requires an understanding of interacting cellular and genetic components. Here, we review how DNA analysis has helped reconstruct the origins of the mosaic, multiresistant mobile elements that have spread through pathogens in the last 60 years. This history helps inform the future, such that resistance might be better managed. Whole-genome sequencing has great potential for epidemiological tracking and for understanding the development of resistance via experimental evolution. DNA analysis also offers the opportunity for constructing databases that record genes of interest, the mobile elements that move these genes, and the cells or species that acquire such genes. Linking these DNA elements to their human and animal hosts and to the environments where they occur should help us establish a more robust ecological and evolutionary framework for controlling and managing resistance. Such efforts need to be well coordinated because, like many other issues that face humanity, antibiotic resistance is a global problem that requires global solutions.
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