title: Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts.
abstract: BACKGROUND
  More than 12,000 simple sequence repeats (SSRs) have been identified in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of phase variation in other pathogenic bacteria, these may function as mutable loci leading to altered protein expression or structure variation. To determine if such alterations are occurring in vivo, the genomes of various single-colony passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced from culture, a mouse, a horse, and two isolates from a single human patient, and the sequence compared to the published B. mallei ATCC 23344 genome sequence.
  
  
  RESULTS
  Forty-nine insertions and deletions (indels) were detected at SSRs in the five passaged strains, a majority of which (67.3%) were located within noncoding areas, suggesting that such regions are more tolerant of sequence alterations. Expression profiling of the two human passaged isolates compared to the strain before passage revealed alterations in the mRNA levels of multiple genes when grown in culture.
  
  
  CONCLUSIONS
  These data support the notion that genome variability upon passage is a feature of B. mallei ATCC23344, and that within a host B. mallei generates a diverse population of clones that accumulate genome sequence variation at SSR and other loci.
authors.affiliation: The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA. cromero@mail.ucf.edu
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Romero
authors.forename: David
authors.initials: D
authors.lastname: DeShazer
authors.forename: Tamara
authors.initials: T
authors.lastname: Feldblyum
authors.forename: Jacques
authors.initials: J
authors.lastname: Ravel
authors.forename: Donald
authors.initials: D
authors.lastname: Woods
authors.forename: H Stanley
authors.initials: HS
authors.lastname: Kim
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Ronning
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
mesh_terms: D000818:Animals; D042726:Burkholderia mallei / Q000235:genetics* / Q000254:growth & development; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016680:Genome, Bacterial / Q000235:genetics; D005896:Glanders / Q000382:microbiology*; D006736:Horses; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018598:Minisatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods