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

Richard T. Okinaka, Erin P. Price, Spenser R. Wolken, Jeffrey M. Gruendike, Wai K. Chung, Talima Pearson, Gary Xie, Chris Munk, Karen K. Hill, Jean Challacombe, Bruce E. Ivins, James M. Schupp, Stephen M. Beckstrom-Sternberg, Arthur Friedlander, Paul Keim

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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.

Original languageEnglish (US)
Article number477
JournalBMC Genomics
Volume12
DOIs
StatePublished - Sep 30 2011

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ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Okinaka, R. T., Price, E. P., Wolken, S. R., Gruendike, J. M., Chung, W. K., Pearson, T., Xie, G., Munk, C., Hill, K. K., Challacombe, J., Ivins, B. E., Schupp, J. M., Beckstrom-Sternberg, S. M., Friedlander, A., & Keim, P. (2011). An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics. BMC Genomics, 12, [477]. https://doi.org/10.1186/1471-2164-12-477