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Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii.

ABSTRACT: Acinetobacter baumannii is an emerging human pathogen and a significant cause of nosocomial infections among hospital patients worldwide. The enormous increase in multidrug resistance among hospital isolates and the recent emergence of pan-drug-resistant strains underscores the urgency to understand how A. baumannii evolves in hospital environments. To this end, we undertook a genomic study of a polyclonal outbreak of multidrug-resistant A. baumannii at the research-based National Institutes of Health Clinical Center. Comparing the complete genome sequences of the three dominant outbreak strain types enabled us to conclude that, despite all belonging to the same epidemic lineage, the three strains diverged before their arrival at the National Institutes of Health. The simultaneous presence of three divergent strains from this lineage supports its increasing prevalence in international hospitals and suggests an ongoing adaptation to the hospital environment. Further genomic comparisons uncovered that much of the diversification that occurred since the divergence of the three outbreak strains was mediated by homologous recombination across 20% of their genomes. Inspection of recombinant regions revealed that several regions were associated with either the loss or swapping out of genes encoding proteins that are exposed to the cell surface or that synthesize cell-surface molecules. Extending our analysis to a larger set of international clinical isolates revealed a previously unappreciated ability of A. baumannii to vary surface molecules through horizontal gene transfer, with subsequent intraspecies dissemination by homologous recombination. These findings have immediate implications in surveillance, prevention, and treatment of A. baumannii infections.

SUBMITTER: Snitkin ES

PROVIDER: S-EPMC3158218 | biostudies-other | 2011 Aug

REPOSITORIES: biostudies-other

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Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii.

Snitkin Evan S ES Zelazny Adrian M AM Montero Clemente I CI Stock Frida F Mijares Lilia L Murray Patrick R PR Segre Julie A JA

Proceedings of the National Academy of Sciences of the United States of America 20110808 33

Acinetobacter baumannii is an emerging human pathogen and a significant cause of nosocomial infections among hospital patients worldwide. The enormous increase in multidrug resistance among hospital isolates and the recent emergence of pan-drug-resistant strains underscores the urgency to understand how A. baumannii evolves in hospital environments. To this end, we undertook a genomic study of a polyclonal outbreak of multidrug-resistant A. baumannii at the research-based National Institutes of ...[more]

PMID: 21825119

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Project description:UnlabelledAcinetobacter baumannii is a Gram-negative bacterium that causes diseases such as pneumonia, bacteremia, and soft tissue infections in hospitalized patients. Relatively little is known about how A. baumannii causes these infections. Thus, we used insertion sequencing (INSeq), a combination of transposon mutagenesis and massively parallel next-generation sequencing, to identify novel virulence factors of A. baumannii. To this end, we generated a random transposon mutant library containing 150,000 unique insertions in A. baumannii strain ATCC 17978. The INSeq analysis identified 453 genes required for growth in rich medium. The library was then used in a murine pneumonia model, and the relative levels of abundance of mutants before and after selection in the mouse were compared. When genes required for growth in rich medium were removed from the analysis, 157 genes were identified as necessary for persistence in the mouse lung. Several of these encode known virulence factors of A. baumannii, such as OmpA and ZnuB, which validated our approach. A large number of the genes identified were predicted to be involved in amino acid and nucleotide metabolism and transport. Other genes were predicted to encode an integration host factor, a transmembrane lipoprotein, and proteins involved in stress response and efflux pumps. Very few genes, when disrupted, resulted in an increase in A. baumannii numbers during host infection. The INSeq approach identified a number of novel virulence determinants of A. baumannii, which are candidate targets for therapeutic interventions.ImportanceA. baumannii has emerged as a frequent cause of serious infections in hospitals and community settings. Due to increasing antibiotic resistance, alternative approaches, such as antivirulence strategies, are desperately needed to fight A. baumannii infections. Thorough knowledge of A. baumannii pathogenicity is essential for such approaches but is currently lacking. With the increasingly widespread use of massively parallel sequencing, a class of techniques known as transposon insertion sequencing has been developed to perform comprehensive virulence screens of bacterial genomes in vivo. We have applied one of these approaches (INSeq) to uncover novel virulence factors in A. baumannii. We identified several such factors, including those predicted to encode amino acid and nucleotide metabolism proteins, an integration host factor protein, stress response factors, and efflux pumps. These results greatly expand the number of A. baumannii virulence factors and uncover potential targets for antivirulence treatments.

Dataset Information

Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii.

Publications

Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii.

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