NIH Research Festival
Burkholderia vietnamiensis is an opportunistic pathogen within the Burkholderia cepacia complex responsible for infections in certain immunocompromised human hosts. In this work, we analyze the evolution of B. vietnamiensis in a patient with IL-12 receptor ÔÅ¢1 deficiency presenting with persistent bloodstream infection for more than 7 months. Bacterial isolates were collected nearly daily over the period of bacteremia (n=183 isolates), providing unprecedented temporal sampling of the underlying population. All isolates were sequenced with Illumina technology, and 24 isolates underwent PacBio long read sequencing to generate highly contiguous assemblies. A composite reference assembly was then constructed from nonredundant complete PacBio contigs derived from individual assemblies and annotated. Single nucleotide variants (SNVs) in individual short read datasets and structural variants in long-read assemblies were identified against this reference. A maximum-likelihood phylogeny computed from the identified SNVs (n=440) revealed a complex underlying population structure with successive bifurcations and distinct clades. Surprisingly, isolates cultured in the first two weeks were distributed broadly throughout the tree, suggesting that this diverse population was present when sampling began. Analysis identified a nonredundant set of 386 insertions relative to the composite reference genome, encoding at least five distinct insertion sequence (IS) elements that were either present in all isolates (ancestral) or only in a subset (differential). We hypothesize that differential IS presence resulted from active IS mobility and that IS insertional mutagenesis contributed to adaptive evolution in the host. Future work will include validation of IS mobility and characterization of transcriptional and fitness consequences of the identified insertions.
Scientific Focus Area: Microbiology and Infectious Diseases
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