DAO 78:115-127 (2007)  -  DOI: https://doi.org/10.3354/dao01859

Sortase inhibitor phenyl vinyl sulfone inhibits Renibacterium salmoninarum adherence and invasion of host cells

Ponnerassery S. Sudheesh1,2, Samuel Crane1,3, Kenneth D. Cain2, Mark S. Strom1,*

1Northwest Fisheries Science Center, NOAA Fisheries Service, 2725 Montlake Boulevard East, Seattle, Washington 98112, USA
2Department of Fish and Wildlife Resources and The Aquaculture Research Institute, University of Idaho, Moscow, Idaho 83844, USA
3Present address: Graduate Center, The City University of New York and the Sackler Institute for Comparative Genomics, American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA
*Corresponding author. Email:

ABSTRACT: Renibacterium salmoninarum, the causative agent of bacterial kidney disease in salmonid fishes, is a Gram-positive diplococcobacillus belonging to the family Micrococcaceae. Analysis of the genome sequence of the bacterium demonstrated the presence of a sortase homolog (srtD), a gene specifying an enzyme found in Gram-positive bacteria and required for covalent anchoring of cell surface proteins. Interference of sortase activity is being examined as a target for therapeutic prevention of infection by several pathogenic Gram-positive bacterial species. In silico analysis identified 8 open reading frames containing sortase recognition motifs, suggesting these proteins are translocated to the bacterial cell wall. The sortase and potential sortase substrate genes are transcribed in R. salmoninarum, suggesting they encode functional proteins. Treatment of R. salmoninarum with phenyl vinyl sulfone (PVS) significantly reduced bacterial adherence to Chinook salmon fibronectin. In addition, the ability of the PVS-treated bacteria to adhere to Chinook salmon embryo cells (CHSE-214) in vitro was dramatically reduced compared to that of untreated bacteria. More importantly, PVS-treated bacteria were unable to invade and replicate within CHSE-214 cells (demonstrated by an intracellular growth assay and by light microscopy). When treated with PVS, R. salmoninarum was not cytopathic to CHSE-214 cells, whereas untreated bacteria produced cytopathology within a few days. These findings clearly show that PVS, a small molecule drug and a known sortase inhibitor, can interfere with the ability of R. salmoninarum to adhere and colonize fish cells, with a corresponding decrease in virulence.

KEY WORDS: Renibacterium salmoninarum · Bacterial kidney disease · Anti-virulence chemotherapy · Adherence · Invasion · Host cell sortase inhibitor · Phenyl vinyl sulfone

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Cite this article as: Sudheesh PS, Crane S, Cain KD, Strom MS (2007) Sortase inhibitor phenyl vinyl sulfone inhibits Renibacterium salmoninarum adherence and invasion of host cells. Dis Aquat Org 78:115-127. https://doi.org/10.3354/dao01859

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