Molecular Medicine Israel

Identifing the host genes of protein toxins Ricin & Pseudomonas exotoxin

Frederic Bard of Singapore’s A*Star Institute of Molecular and Cell Biology , November 2011
How toxins hijack cellular processes-
Identification of the host genes that two notorious protein toxins require to invade human cells could lead to the development of novel antidotes Genes that allow the deadly protein toxins Ricin and Pseudomonas exotoxin to enter human cells and wreak havoc have been identified by a research team led by Frederic Bard of Singapore’s A*Star Institute of Molecular and Cell Biology.
Ricin prepared from beans of the castor plant Ricinus communis is a potential biological weapon. Pseudomonas exotoxin, however, is produced and secreted by the opportunistic bacterial pathogen Pseudomonas aeruginosa, which infects patients who have cystic fibrosis, compromised immune systems, or burn wounds. Once inside cells, both toxins cause damage by disrupting protein synthesis, but little is known about the precise mechanisms by which they gain entry to hijack cellular processes.
Bard and team therefore scoured the human genome for genes needed for intoxication using a technique known as RNAi screening. Despite showing limited overlap in host genes required by Ricin and Pseudomonas exotoxin to gain entry to cells, the researchers found that many of the necessary factors, some of them involved in membrane traffic, are nevertheless present in similar cellular compartments and structures. They concluded that the two toxins exploit intertwined pathways that converge and diverge at multiple points.
The researchers hope that their findings will lead to new ways to thwart these dangerous cell invaders.

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