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Journal of Bacteriology, November 2008, p. 6970-6982, Vol. 190, No. 21
0021-9193/08/$08.00+0     doi:10.1128/JB.00721-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genome Sequence of the Fish Pathogen Renibacterium salmoninarum Suggests Reductive Evolution away from an Environmental Arthrobacter Ancestor ^,

Gregory D. Wiens,^1, Daniel D. Rockey,^2, Zaining Wu,³ Jean Chang,³ Ruth Levy,³ Samuel Crane,⁴ Donald S. Chen,⁴ Gina R. Capri,² Jeffrey R. Burnett,² Ponnerassery S. Sudheesh,⁴ Matthew J. Schipma,⁵ Henry Burd,⁵ Anamitra Bhattacharyya,⁵ Linda D. Rhodes,⁴ Rajinder Kaul,³ and Mark S. Strom^4*

USDA-ARS-National Center for Cool and Coldwater Aquaculture, Kearneysville, West Virginia 25430,¹ Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331,² Division of Medical Genetics, Department of Medicine, and University of Washington Genome Center, University of Washington, Seattle, Washington 98195,³ Northwest Fisheries Science Center, NOAA Fisheries Service, Seattle, Washington 98112,⁴ Integrated Genomics, Inc., Chicago, Illinois 60612⁵

Received 21 May 2008/ Accepted 12 August 2008

Renibacterium salmoninarum is the causative agent of bacterial kidney disease and a significant threat to healthy and sustainable production of salmonid fish worldwide. This pathogen is difficult to culture in vitro, genetic manipulation is challenging, and current therapies and preventative strategies are only marginally effective in preventing disease. The complete genome of R. salmoninarum ATCC 33209 was sequenced and shown to be a 3,155,250-bp circular chromosome that is predicted to contain 3,507 open-reading frames (ORFs). A total of 80 copies of three different insertion sequence elements are interspersed throughout the genome. Approximately 21% of the predicted ORFs have been inactivated via frameshifts, point mutations, insertion sequences, and putative deletions. The R. salmoninarum genome has extended regions of synteny to the Arthrobacter sp. strain FB24 and Arthrobacter aurescens TC1 genomes, but it is approximately 1.9 Mb smaller than both Arthrobacter genomes and has a lower G+C content, suggesting that significant genome reduction has occurred since divergence from the last common ancestor. A limited set of putative virulence factors appear to have been acquired via horizontal transmission after divergence of the species; these factors include capsular polysaccharides, heme sequestration molecules, and the major secreted cell surface antigen p57 (also known as major soluble antigen). Examination of the genome revealed a number of ORFs homologous to antibiotic resistance genes, including genes encoding β-lactamases, efflux proteins, macrolide glycosyltransferases, and rRNA methyltransferases. The genome sequence provides new insights into R. salmoninarum evolution and may facilitate identification of chemotherapeutic targets and vaccine candidates that can be used for prevention and treatment of infections in cultured salmonids.

Published ahead of print on 22 August 2008.

Supplemental material for this article may be found at http://jb.asm.org/.

G.D.W. and D.D.R. contributed equally to this research and are co-first authors.