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

2021 ◽  
Vol 18 (3) ◽  
pp. 591-601
Author(s):  
Om Kumar ◽  
G Keerthana ◽  
Ashitha B Arun ◽  
Ananya Joliholi ◽  
Lokesh Ravi

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.

Aquaculture ◽  
2007 ◽  
Vol 269 (1-4) ◽  
pp. 114-122 ◽  
Author(s):  
David Bruno ◽  
Bertrand Collet ◽  
Anna Turnbull ◽  
Rachel Kilburn ◽  
Amanda Walker ◽  
...  

2006 ◽  
Vol 72 (4) ◽  
pp. 2672-2678 ◽  
Author(s):  
Alison M. Coady ◽  
Anthony L. Murray ◽  
Diane G. Elliott ◽  
Linda D. Rhodes

ABSTRACT Renibacterium salmoninarum, a gram-positive diplococcobacillus that causes bacterial kidney disease among salmon and trout, has two chromosomal loci encoding the major soluble antigen (msa) gene. Because the MSA protein is widely suspected to be an important virulence factor, we used insertion-duplication mutagenesis to generate disruptions of either the msa1 or msa2 gene. Surprisingly, expression of MSA protein in broth cultures appeared unaffected. However, the virulence of either mutant in juvenile chinook salmon (Oncorhynchus tshawytscha) by intraperitoneal challenge was severely attenuated, suggesting that disruption of the msa1 or msa2 gene affected in vivo expression.


2006 ◽  
Vol 63 (12) ◽  
pp. 2793-2808 ◽  
Author(s):  
Jeffrey J Hard ◽  
Diane G Elliott ◽  
Ronald J Pascho ◽  
Dorothy M Chase ◽  
Linda K Park ◽  
...  

We evaluated genetic variation in ability of Chinook salmon (Oncorhynchus tshawytscha) to resist two bacterial pathogens: Renibacterium salmoninarum, the agent of bacterial kidney disease (BKD), and Listonella anguillarum, an agent of vibriosis. After measuring R. salmoninarum antigen in 499 adults by enzyme-linked immunosorbent assay (ELISA), we mated each of 12 males with high or low antigen levels to two females with low to moderate levels and exposed subsets of their progeny to each pathogen separately. We found no correlation between R. salmoninarum antigen level in parents and survival of their progeny following pathogen exposure. We estimated high heritability for resistance to R. salmoninarum (survival h2 = 0.890 ± 0.256 (mean ± standard error)) independent of parental antigen level, but low heritability for resistance to L. anguillarum (h2 = 0.128 ± 0.078). The genetic correlation between these survivals (rA = –0.204 ± 0.309) was near zero. The genetic and phenotypic correlations between survival and antigen levels among surviving progeny exposed to R. salmoninarum were both negative (rA = –0.716 ± 0.140; rP = –0.378 ± 0.041), indicating that variation in antigen level is linked to survival. These results suggest that selective culling of female broodstock with high antigen titers, which is effective in controlling BKD in salmon hatcheries, will not affect resistance of their progeny.


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