title: A novel method of consensus pan-chromosome assembly and large-scale comparative analysis reveal the highly flexible pan-genome of Acinetobacter baumannii.
abstract: BACKGROUND
  Infections by pan-drug resistant Acinetobacter baumannii plague military and civilian healthcare systems. Previous A. baumannii pan-genomic studies used modest sample sizes of low diversity and comparisons to a single reference genome, limiting our understanding of gene order and content. A consensus representation of multiple genomes will provide a better framework for comparison. A large-scale comparative study will identify genomic determinants associated with their diversity and adaptation as a successful pathogen.
  
  
  RESULTS
  We determine draft-level genomic sequence of 50 diverse military isolates and conduct the largest bacterial pan-genome analysis of 249 genomes. The pan-genome of A. baumannii is open when the input genomes are normalized for diversity with 1867 core proteins and a paralog-collapsed pan-genome size of 11,694 proteins. We developed a novel graph-based algorithm and use it to assemble the first consensus pan-chromosome, identifying both the order and orientation of core genes and flexible genomic regions. Comparative genome analyses demonstrate the existence of novel resistance islands and isolates with increased numbers of resistance island insertions over time, from single insertions in the 1950s to triple insertions in 2011. Gene clusters responsible for carbon utilization, siderophore production, and pilus assembly demonstrate frequent gain or loss among isolates.
  
  
  CONCLUSIONS
  The highly variable and dynamic nature of the A. baumannii genome may be the result of its success in rapidly adapting to both abiotic and biotic environments through the gain and loss of gene clusters controlling fitness. Importantly, some archaic adaptation mechanisms appear to have reemerged among recent isolates.
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Agnes P
authors.initials: AP
authors.lastname: Chan
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Granger
authors.initials: G
authors.lastname: Sutton
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: DePew
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Radha
authors.initials: R
authors.lastname: Krishnakumar
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Yongwook
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Emerging Bacterial Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Xiao-Zhe
authors.initials: XZ
authors.lastname: Huang
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Beck
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Harkins
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Kim
authors.affiliation: Multidrug-resistant organism Repository and Surveillance Network, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Emil P
authors.initials: EP
authors.lastname: Lesho
authors.affiliation: Department of Emerging Bacterial Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Mikeljon P
authors.initials: MP
authors.lastname: Nikolich
authors.affiliation: J. Craig Venter Institute (JCVI), Rockville, MD, USA. dfouts@jcvi.org.
authors.forename: Derrick E
authors.initials: DE
authors.lastname: Fouts
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D000465:Algorithms; D002876:Chromosomes, Bacterial; D023061:Gene Order; D020043:Genes, Essential; D016680:Genome, Bacterial; D044404:Genomic Islands; D023281:Genomics / Q000379:methods*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008889:Military Personnel; D014774:Virulence / Q000235:genetics