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Research Article

Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists

  • Steven E. Schutzer mail,

    schutzer@umdnj.edu

    Affiliation: Department of Medicine, University of Medicine and Dentistry - New Jersey Medical School, Newark, New Jersey, United States of America

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  • Linda R. K. Schlater,

    Affiliation: United States Department of Agriculture, Ames, Iowa, United States of America

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  • Catherine M. Ronning,

    Affiliation: J. Craig Venter Institute, Rockville, Maryland, United States of America

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  • David DeShazer,

    Affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America

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  • Benjamin J. Luft,

    Affiliation: Department of Medicine, State University of New York, Stony Brook, New York, United States of America

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  • John J. Dunn,

    Affiliation: Biology Department, Brookhaven National Laboratory, Upton, New York, United States of America

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  • Jacques Ravel,

    Affiliations: Institute for Genome Sciences, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America

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  • Claire M. Fraser-Liggett,

    Affiliations: Institute for Genome Sciences, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America

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  • William C. Nierman

    Affiliations: J. Craig Venter Institute, Rockville, Maryland, United States of America, Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington, D. C., United States of America

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  • Published: April 30, 2008
  • DOI: 10.1371/journal.pone.0002058
  • Published in PLOS ONE

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Referee Comments: Referee 1

Posted by PLoS_ONE_Group on 05 May 2008 at 16:22 GMT

Referee 1's Review:

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication, the manuscript has been revised in light of these comments and to address other editorial requirements.
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This manuscript describes the genomic sequence of an avirulent isolate of Burkholderia mallei, the causative agent of glanders in horses and humans, and an important biothreat agent. The sequencing of an avirulent B. mallei is an essential contribution ot research on this important bacterial species. The principal finding of this work is the absence of a type III secretion system in this isolate, a feature previously shown to be essential for virulence in rodent models and present in a virulent B. mallei isolate sequence.

1. The sequence and basic analysis is appropriate and supports the author's conclusions that deletions of much of the type III secretions system and other genes are present in the avirulent compared to the virulent B. mallei isolate. A more thorough description of the comparative sequence analysis, including summary data regarding sequence homology between genes present in both isolates, would be useful however, as other more subtle changes could also contribute to virulence.
2. While the absence of a type III secretion apparatus could be responsible for avirulence, there are some caveats to this conclusion. First, the challenge experiment did not include a positive control, a particularly important omission given the limited experience with equine challenge present in the literature. The authors rightly indicate that the original challenge was not intended as a virulence experiment. However, virulence or the lack thereof is a key element of the current work and deserves further discussion. Second, sequence changes other than loss of the type III secretion system could be entirely responsible for avirulence in horses. A complementation experiment, in which restoration of the type III apparatus restores virulence, is required to definitively confirm this conclusion, and to rule out other factors. Neither of these caveats diminishes the importance of the data presented in this paper but they should be discussed.
3. The authors discuss the utility of an avirulent B. mallei strain for use in research outside of Select Agent regulations, which is certainly true if avirulence can be ascertained. However, they fail to discuss the potential of this strain as a vaccine. The isolate is capable of inducing antibodies, shown in rodent models to confer passive protection against B. mallei. The possible utility of this strain as a vaccine candidate or parental strain should be addressed.

Some minor points. There are spelling and typographic errors that should be corrected. The use of "TTSS" is ambiguous as it could mean either type three or type two secretion systems. The commonly used "T3S system" is preferred.