Construction of 3D Model of Protein Drug Targets for Renibacterium Salmoninarum - A Bacterial Pathogen Causing Bacterial Kidney Disease in Young Salmonid Fish

The aim of this study is to construct 3D models of potential drug targets for the Bacterial Kidney Disease (BKD) causing pathogen Renibacterium salmoninarum. The bacterial pathogen Renibacterium salmoninarum was selected for homology modeling studies since there were no known protein structures of the organism reported in the NCBI database. The reported protein sequences were run through DrugBank to pick out drug-targets. Online databases and web tools such as PMDB, UniProt, Drug Bank, and SwissModel were employed in this analysis. An aggregate of 412 protein sequences were identified as potential drug targets and were retrieved from the UniProt. Homology models of the protein sequences were constructed using the SwissModel database for all 412 proteins. These were then refined through a protein blast and Ramachandran plot analysis. Out of the 412 constructed models, 143 models were of reliable quality. These were then submitted to the PMDB database for further reference. To demonstrate the application of these constructed models, protein-ligand docking analysis using Auto Dock Vina was performed. Among the antibiotics that were tested against their known drug targets, trimethoprim demonstrated significant potential for the inhibition of R. salmoninarum’s dihydrofolate reductase protein, with a binding energy of -9.06 Kcal/mol and with the formation of 3 hydrogen bonds. Therefore through protein-ligand docking studies and the construction of 3D models of protein drug targets, Trimethoprim is proposed as a solution to the Bacterial Kidney Disease (BKD) problem in salmonid fishes. Further in-vitro evidences are in demand to prove this hypothesis.

Molecular detection of Renibacterium salmoninarum in rainbow trout (Oncorhynchus mykiss) from Poland

Renibacterium salmoninarum causes bacterial kidney disease mainly in salmonid fish. Oligonucleotide primers incorporating R. salmoninarum unique sequences were designed to amplify a 501 bp region of the gene encoding a 57 kDa soluble extra-cellular protein. The primers did not amplify other wide varieties of aquatic or piscine bacteria Aeromonas salmonicida or Yersinia ruckeri. This assay provides a molecular description and definitive identification of R. salmoninarum in Poland.

Renibacterium salmoninarum—The Causative Agent of Bacterial Kidney Disease in Salmonid Fish

Renibacterium salmoninarum is one of the oldest known bacterial pathogens of fish. This Gram-positive bacterium is the causative agent of bacterial kidney disease, a chronic infection that is mostly known to infect salmonid fish at low temperatures. Externally, infected fish can display exophthalmia as well as blebs on the skin and ulcerations alongside haemorrhages at the base of the fins and alongside the lateral line. Internally, the kidney, heart, spleen and liver can show signs of swelling. Granulomas can be seen on various internal organs, as can haemorrhages, and the organs can be covered with a false membrane. Ascites can also accumulate in the abdominal cavity. The bacterium is generally cultivated on specialized media such as kidney disease medium-1 (KDM-1), KDM-2 and selective kidney disease medium (SKDM), and a diagnostic is performed using molecular tools such as PCRs or real-time quantitative PCRs (RT-qPCRs). Several virulence mechanisms have been identified in R. salmoninarum, in particular the protein p57 that is known to play a role in both agglutination and immunosuppression of the host’s defense mechanisms. Control of the disease is difficult; the presence of asymptomatic carriers complicates the eradication of the disease, as does the ability of the bacterium to gain entrance inside the eggs. Bacterin-killed vaccines have proven to be of doubtful efficacy in controlling the disease, and even more recent application of a virulent environmental relative of R. salmoninarum is of limited efficacy. Treatment by antibiotics such as erythromycin, azithromycin and enrofloxacin can be effective but it is slow and requires prolonged treatment. Moreover, antibiotic-resistant strains have been reported. Despite being known for a long time, there is still much to be discovered about R. salmoninarum, notably regarding its virulence mechanisms and its vaccine potential. Consequently, these gaps in knowledge continue to hinder control of this bacterial disease in aquaculture settings.

Efficacy of Erymicin 200 Injections for Reducing Renibacterium salmoninarum and Controlling Vertical Transmission in an Inland Rainbow Trout Brood Stock

Bacterial Kidney Disease, caused by Renibacterium salmoninarum (Rs), is widespread and can cause significant mortality at most life stages in infected salmonids. Rs is commonly found in inland trout, which can be carriers of the bacterium. Lethal spawns can be used to control vertical transmission to progeny through the culling of eggs from infected parents, but can be costly, time-consuming, and can negatively impact important and rare brood stocks. Erymicin 200 is an Investigational New Animal Drug (INAD) intended to reduce Rs levels in hatchery brood stocks and control vertical transmission to progeny. We tested the efficacy of Erymicin 200 injections in a positive, hatchery-resident rainbow trout (Oncorhynchus mykiss) brood stock in Colorado, USA. Brood fish age two and three were injected with 25 mg per kg of body weight Erymicin 200 three times prior to spawning. Erymicin 200 was effective in reducing Rs to below detectable levels in treated fish. However, both negative treated and control brood fish produced positive progeny, suggesting that Erymicin 200 did not prevent the vertical transmission of Rs.

First report of bacterial kidney disease in coho salmon Oncorhynchus kisutch in Russia

This paper describes the first case of bacterial kidney disease (BKD) to be identified in coho salmon Oncorhynchus kisutch in Russia. The fish in question was caught in Lake Bolshoi Vilyui on the Kamchatka Peninsula. The diseased fish had foci of granulomatous inflammation in the kidneys. The diagnosis was confirmed by isolating the bacterium Renibacterium salmoninarum from kidney tissue in pure culture, and by determining the partial 16S RNA gene sequence of the isolate. This is the first detection of this pathogen in the genus Oncorhynchus in Russia, and detection of BKD in coho salmon indicates that the pathogen is present in the natural fish populations of Kamchatka. Therefore, it will be necessary to conduct screening studies of mature salmon selected for artificial reproduction, for the presence of BKD signs and asymptomatic infection with R. salmoninarum, which will allow us to estimate the prevalence of the pathogen.