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 ␤-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.

Fish living in the wild as well as reared in the aquaculture facilities are susceptible to infectious diseases caused by a phylogenetically diverse collection of bacterial pathogens. Control and treatment options using vaccines and drugs are either inadequate, inefficient, or impracticable. The classical approach in studying fish bacterial pathogens has been looking at individual or few virulence factors. Recently, genome sequencing of a number of bacterial fish pathogens has tremendously increased our understanding of the biology, host adaptation, and virulence factors of these important pathogens. This paper attempts to compile the scattered literature on genome sequence information of fish pathogenic bacteria published and available to date. The genome sequencing has uncovered several complex adaptive evolutionary strategies mediated by horizontal gene transfer, insertion sequence elements, mutations and prophage sequences operating in fish pathogens, and how their genomes evolved from generalist environmental strains to highly virulent obligatory pathogens. In addition, the comparative genomics has allowed the identification of unique pathogen-specific gene clusters. The paper focuses on the comparative analysis of the virulogenomes of important fish bacterial pathogens, and the genes involved in their evolutionary adaptation to different ecological niches. The paper also proposes some new directions on finding novel vaccine and chemotherapeutic targets in the genomes of bacterial pathogens of fish.

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