JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
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Quantitative assessment of insertion sequence impact on bacterial genome architecture.

Insertion sequence (IS) elements are important mediators of genome plasticity and can lead to phenotypic changes with evolutionary significance. In multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae , IS elements have contributed significantly to the mobilization of genes that encode resistance to antimicrobial drugs. A systematic analysis of IS elements is needed for a more comprehensive understanding of their evolutionary impact. We developed a computational approach (ISseeker) to annotate IS elements in draft genome assemblies and applied the method to analysis of IS elements in all publicly available A. baumannii (>1000) and K. pneumoniae (>800) genome sequences, in a phylogenetic context. Most IS elements in A. baumannii genomes are species-specific IS Aba elements, whereas K. pneumoniae genomes contain significant numbers of both IS Kpn elements and elements that are found throughout the Enterobacteriaceae. A. baumannii genomes have a higher density of IS elements than K. pneumoniae, averaging ~33 vs ~27 copies per genome. In K. pneumoniae , several insertion sites are shared by most genomes in the ST258 clade, whereas in A. baumannii , different IS elements are abundant in different phylogenetic groups, even among closely related Global Clone 2 strains. IS elements differ in the distribution of insertion locations relative to genes, with some more likely to disrupt genes and others predominantly in intergenic regions. Several genes and intergenic regions had multiple independent insertion events, suggesting that those events may confer a selective advantage. Genome- and taxon-wide characterization of insertion locations revealed that IS elements have been active contributors to genome diversity in both species.

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