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Despite its great importance in contributing to our understanding of human disease, there is limited knowledge regarding pathogen evolution within a host, or a population during patient-to-patient transmission. This has been hampered, in part, by the lack of sufficiently comprehensive methods to capture pathogen microevolution within hosts. Here we utilize next generation sequencing to explore the genomic variation within isolates of an epidemic lineage of the opportunistic pathogen Burkholderia cenocepacia, taken from patients over the course of 20 years. Detailed genomic analyses revealed 1) many fine scale differences in genes of interest for virulence or treatment options, such as mutations in antibiotic resistance genes, 2) signs of convergent evolution, and 3) evidence of a general trend toward genome streamlining as an evolutionary strategy in this host-adapted lineage. Our findings suggest that the highly pathogenic B. cenocepacia ET-12 lineage is composed of distinct sublineages that can be independently acquired from environmental reservoirs. These findings have broad implications with respect to the use of sequencing for epidemiological surveillance, infection control, and outbreak investigations. |