Researchers create virus-resistant, safely restrained E. coli for medical, industrial applications

In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild.

The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels. Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

"We believe we have developed the first technology to design an organism that can't be infected by any known virus," said the study's first author, Akos Nyerges, research fellow in genetics in the lab of George Church in the Blavatnik Institute at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering.

"We can't say it's fully virus-resistant, but so far, based on extensive laboratory experiments and computational analysis, we haven't found a virus that can break it," Nyerges said. The work also provides the first built-in safety measure that prevents modified genetic material from being incorporated into natural cells, he said.

The key lay in transfer RNAs, or tRNAs. Each tRNA's role is to recognize a specific codon and add the corresponding amino acid to a protein that's being built. For instance, the codon TCG tells its matching tRNA to attach the amino acid serine.

In this case, the Cambridge team had deleted TCG along with sister codon TCA, which also calls for serine. The team had also removed the corresponding tRNAs. The HMS team now added new, trickster tRNAs in their place. When these tRNAs see TCG or TCA, they add leucine instead of serine. "Leucine is about as different from serine as you can get, physically and chemically," said Nyerges.

Image source: Behnoush Hajian.