Open Access Research article

Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts

Claudia M Romero1, David DeShazer2, Tamara Feldblyum1, Jacques Ravel1, Donald Woods3, H Stanley Kim1, Yan Yu1, Catherine M Ronning1* and William C Nierman14

Author Affiliations

1 The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA

2 Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA

3 Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta T2N 4N1, Canada

4 The George Washington University School of Medicine, Departmentof Biochemistry and Molecular Biology, 2300 Eye Street NW, Washington, DC 20037, USA

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BMC Genomics 2006, 7:228  doi:10.1186/1471-2164-7-228

Published: 5 September 2006

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.

Conclusion

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.