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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

AUTHORS

Richard T Okinaka, Erin P Price, Spenser R Wolken, Jeffrey M Gruendike, Wai Kwan 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

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. More... »

PAGES

477

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2164-12-477

DOI

http://dx.doi.org/10.1186/1471-2164-12-477

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049097109

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21962024


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