Treatment for E. coli may be closer than we think

The spider-like icosahedral shape is an abstract depiction of the Shiga toxin bacteriophage with a red genome, stylised as the puppet master of a potentially deadly EHEC infection. Credit: Eliza Wolfson/UNSW Sydney

Treatment against a certain strain of E. coli which causes serious intestinal infections may become a reality.

Although a lesser common foodborne disease, the strain, known as enterohemorrhagic E. coli (EHEC), remains a huge food safety concern as it can be extremely severe and even fatal.

Only in 2011 did Germany witness a big outbreak (spread mostly via contaminated sprouts), whereby over 4,000 people were infected and 50 died.

The pathogen releases Shiga toxins during infection, resulting in kidney and neurological damage. A team from UNSW Sydney has now discovered a new molecular pathway that controls this Shiga toxin production. This is a big step forwards, as currently there is no commercially available treatment for EHEC.

Dr Jai Tree. Credit: UNSW Sydney

 “Antibiotic treatment of these infections is generally not recommended because antibiotics stimulate production of the Shiga toxin, leading to an increased risk of kidney failure, neurological damage, and death,” Dr Jai Tree, the study’s senior author, said.

“The new pathway that we have found reduces toxin production and is not expected to be stimulated by antibiotic treatment. So, our results identify a potential new target for the development of drugs that can suppress Shiga toxin production during EHEC infection.”

First new pathway discovered in 20 years

Along with being a momentous step forwards, Dr Tree said that the findings were surprising due to Shiga toxin genes being so well studied in the past. There have been nearly 7,000 published studies in the last 40 years; with this latest finding the first discovery of a new pathway that controls the Shiga toxins in almost two decades.

“In 2001, researchers at Tufts and Harvard universities first showed how production of the Shiga toxin was controlled by a bacterial virus, known as a bacteriophage, within the genome,” explained Dr Tree. This has been the only known pathway that controls Shiga toxin production for almost two decades.

“We have extended that 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 – a working copy of the gene,” he continued.

“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.

“Only recently have we been able use advances in RNA sequencing technology to detect the presence of the new regulatory non-coding RNA embedded within the Shiga toxin messenger RNA.

“This new regulatory non-coding RNA had been hiding in plain sight for almost 20 years.”

But it’s still early days, Dr Tree added. “We need to conduct a lot more research to understand if our findings apply to a broad range of clinical EHEC isolates and to both types of Shiga toxins produced by human EHEC isolates.”