Monday, September 12, 2022

First known bacteria derived RNA-targeting toxin to kill bacteria

Good news! A possible breakthrough in developing a new class of antibiotics. How bacteria kill other bacteria! We still can learn so much from nature!

"Scientists at McMaster University have identified a toxin used by bacteria to kill other bacteria through a never-before-seen mechanism. The toxin is the first found to directly target RNA molecules in what the team describes as “a total assault on the cell,” which could lead to a new class of antibiotics. ..."

"... The study ... shows that the bacterial pathogen Pseudomonas aeruginosa, known to cause hospital-acquired infections such as pneumonia, secretes a toxin that has evolved to kill other species of bacteria. ..."

From the abstract:
"ADP-ribosyltransferases (ARTs) were among the first identified bacterial virulence factors. Canonical ART toxins are delivered into host cells where they modify essential proteins, thereby inactivating cellular processes and promoting pathogenesis. Our understanding of ARTs has since expanded beyond protein-targeting toxins to include antibiotic inactivation and DNA damage repair. Here, we report the discovery of RhsP2 as an ART toxin delivered between competing bacteria by a type VI secretion system of Pseudomonas aeruginosa. A structure of RhsP2 reveals that it resembles protein-targeting ARTs such as diphtheria toxin. Remarkably, however, RhsP2 ADP-ribosylates 2′-hydroxyl groups of double-stranded RNA, and thus, its activity is highly promiscuous with identified cellular targets including the tRNA pool and the RNA-processing ribozyme, ribonuclease P. Consequently, cell death arises from the inhibition of translation and disruption of tRNA processing. Overall, our data demonstrate a previously undescribed mechanism of bacterial antagonism and uncover an unprecedented activity catalyzed by ART enzymes."

First known RNA-targeting toxin launches "total assault" to kill bacteria






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