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Open Access Research article

An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics

Richard T Okinaka12*, Erin P Price1, Spenser R Wolken1, Jeffrey M Gruendike1, Wai Kwan Chung1, Talima Pearson1, Gary Xie2, Chris Munk2, Karen K Hill2, Jean Challacombe2, Bruce E Ivins3, James M Schupp4, Stephen M Beckstrom-Sternberg14, Arthur Friedlander3 and Paul Keim124

Author Affiliations

1 Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ 86011, USA

2 Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA

3 Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA

4 Pathogen Genomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA

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BMC Genomics 2011, 12:477  doi:10.1186/1471-2164-12-477

Published: 30 September 2011

Abstract

Background

An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990.

Results

We demonstrate that despite these B. anthracis features, the isolate is severely attenuated in a guinea pig model. This prompted whole genome sequencing and closure. The comparative analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b) CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15 other isolates; c) the genome of CDC 684 contains a large chromosomal inversion that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual spatial orientation of the origin of replication (ori) to the termination of replication (ter) from 180° in wild-type B. anthracis to 120° in CDC 684 and e) this isolate also has altered growth kinetics in liquid media.

Conclusions

We propose two alternative hypotheses explaining the attenuated phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter relationship in CDC 684 has altered its DNA replication and/or transcriptome processes resulting in altered growth kinetics and virulence capacity. Hypothesis 2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has altered the expression of a regulatory element or other genes necessary for virulence.