Novel Drug Target for Deadly E.Coli Strain on its Way: RNA Sequencing, the Protagonist

There are certain types of E.coli infections that can prove to be fatal. However, the recent advancements in RNA sequencing have revealed a previously hidden molecular pathway that is a potential drug target for such infection.

While majority of foodborne E.coli infections show symptoms including vomiting, nausea, and/or diarrhea, there is a strain that can be fatal. Enterohermorrhagic E.coli (EHEC), mainly found in the feces of cows and sheep, releases Shiga toxins during infection, which can even result in neurological and kidney damage. Thus, the recently discovered molecular pathway not only controls but also reduces the production of Shiga toxin.

Conflicting with the most infections, antibiotics in this case, have been found to worsen EHEC by exciting Shiga toxin production. This, as mentioned above, could multiply the risk of organ failure and even death. But in the words of study author- Jai Tree, who is also a professor at the University of New South Wales (Australia); the new pathway is not expected to be stimulated by antibiotics. This is definitely a key finding, since there is currently no commercially available treatment for Enterohermorrhagic E.coli.

Tree’s findings overturn the traditional beliefs regarding the pathways that control Shiga toxins. In 2001, researchers at Tufts and Harvard were the first to show how production of the Shiga toxin is controlled by a bacteriophage within the genome. For nearly two decades, this has been the only known pathway—until now.

“We have extended this work to show a new mechanism of toxin control that is, surprisingly, buried within the start of the DNA sequence that encodes the Shiga-toxin messenger RNA,” explained Tree, whose paper was recently published in PNAS. “We discovered a very short piece of the toxin messenger RNA is made into a regulatory non-coding RNA that silences the toxin and promotes growth of the pathogen.”

“Our results identify a potential new target for the development of drugs that can suppress Shiga toxin production during EHEC infection. New treatments could therefore reduce the risk of kidney damage, neurological complications and death. We look forward to testing these new interventions in the next stage of our research,” Tree concluded.