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Title: Genome sequence of the fish pathogen Renibacterium salmoninarum suggests reductive evolution away from an environmental Arthrobacter ancestor.

Author
item Wiens, Gregory - Greg
item ROCKEY, D - OREGON STATE UNIVERSITY
item WU, Z - UNIVERSITY OF WASHINGTON
item CHANG, J - UNIVERSITY OF WASHINGTON
item LEVY, R - UNIVERSITY OF WASHINGTON
item CRANE, S - NORTHWEST FISHERIES SCIEN
item CHEN, D - NORTHWEST FISHERIES SCIEN
item CAPI, G - OREGON STATE UNIVERSITY
item BURNETT, J - OREGON STATE UNIVERSITY
item PONNERASSARY, S - NORTHWEST FISHERIES SCIEN
item SCHIMPMA, M - INTEGRATED GENOMICS, INC
item BURD, H - NORTHEST FISHERIES SCIEN
item BHATTACHARYYA, A - UNIVERSITY OF WASHINGTON
item RHODES, L - NORTHWEST FISHERIES SCIEN
item KAUL, R - UNIVERSITY OF WASHINGTON
item STROM, M - NORTHWEST FISHERIES SCIEN

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2008
Publication Date: 8/22/2008
Citation: Wiens, G.D., Rockey, D.D., Wu, Z., Crane, S., Chen, D.S., Capri, G.R., Burnett, J.R., Ponnerassary, S., Schimpma, M.J., Burd, H., Bhattacharyya, A., Rhodes, L.D., Strom, M.S. 2008. The genome sequence of Renibacterium salmoninarum suggests reductive evolution away from an environmental Arthrobacter ancestor. Journal of Bacteriology. 190(21):6970-6982.

Interpretive Summary: Renibacterium salmoninarum (Rs) is the causative agent of bacterial kidney disease and a significant threat to the healthy and sustainable production of salmonid fish in the United States. The pathogen is difficult to culture in vitro, genetics for the organism are challenging, and current therapies and preventative strategies are only marginally effective in preventing disease. Here, we report the complete genome sequence of Rs strain ATCC 33209. The genome is composed of a single circular chromosome comprised of over 3.1 million base pairs and 3,507 putative genes. Whole-genome comparisons indicated that the closest known relative is within the genera Arthrobacter which are ubiquitous soil microorganisms. There are large regions of similarity between Rs and Arthrobacter genomes; however, there are also striking differences as the genome of Rs is about one-third smaller, there are no plasmids, and a surprising high percentage of Rs genes (21%) are inactivated due to mutation. These characteristics suggest Rs has undergone extensive genome changes in the process of evolving from a putative soil microorganism into a fish pathogen. The genome sequence has allowed the identification of chemotherapeutic targets and vaccine candidates that may have future utility in preventing or treating infections in cultured salmonids.

Technical Abstract: Renibacterium salmoninarum (Rs) is the causative agent of bacterial kidney disease and a significant threat to the healthy and sustainable production of salmonid fish worldwide. The 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 circular chromosome of 3,155,250 bp that is predicted to encode 3,507 open-reading frames (ORFs). There are a total of 80 copies of three different insertion sequence (IS) elements interspersed throughout the genome. Approximately 21% of the predicted ORFs have been inactivated via frameshifts, point mutations, insertion sequences and putative deletions. The Rs genome has extended regions of synteny to Arthrobacter sp. FB24 and A. aurescens TC1, but is approximately 1.9 Mb smaller than both Arthrobacter spp. genomes with a lower G+C content, suggesting 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 include capsular polysaccharides, heme sequestration molecules, and the major secreted cell surface antigen p57 (also known as major soluble antigen). Examination of the genome reveals a number of ORFs homologous to antibiotic resistance genes, including ß-lactamases, efflux proteins, macrolide glycosyltransferases, and ribosomal RNA methyltransferases. The genome sequence provides new insights into Rs evolution and may facilitate identification of chemotherapeutic targets and vaccine candidates for future utility in prevention and treatment of infections in cultured salmonids.