Some viruses can infect and kill a recoded 贰蝉肠丑别谤颈肠丑颈补听肠辞濒颈 bacterium that was supposedly resistant to all viral infections, but further changes have made the bacterium much more virus-resistant.
Many chemicals and drugs, such as insulin, are produced by growing genetically engineered E. coli in large vats, but bacteria-infecting viruses called bacteriophages can wreak havoc. 鈥淚f a single bacteriophage gets into these fermenters, in just hours everything is dead,鈥� says at Harvard University.
Several groups are therefore developing virus-resistant bacteria. Nyerges won鈥檛 go so far as to say that his team鈥檚 souped-up E. coli strain could never be infected, 鈥渂ut it鈥檚 highly unlikely鈥�, he says.
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The ability of viruses to infect cells depends on the fact that all living organisms use the same genetic code, with only a few variations. The idea is to change this code.
DNA in cells contains recipes for making proteins, which are strings of amino acids. Three-letter bits of DNA, called codons, code for a specific amino acid or a 鈥渟top making this protein鈥� signal.
In cells鈥� protein-making factories, molecules called transfer RNAs, or tRNAs, recognise each codon and add the appropriate amino acid to the protein chain.
Overall, there are 20 amino acids and 64 codons, which makes for a lot of redundancy. For instance, six different codons code for the amino acid serine.
In 2019, a team led by at the University of Cambridge resynthesised the DNA of an E. coli bacterium from scratch to change all instances of two serine codons to one of the other serine codons. The researchers did the same with one stop codon. This led to an E. coli strain they called Syn61, because it uses only 61 codons.
Syn61 wasn鈥檛 virus resistant because tRNAs that recognise the eliminated codons are still present, meaning viral genes are still translated into proteins. In an effort to overcome this, Chin and his team deleted these tRNAs. 鈥淭he resulting strain provides complete resistance to a cocktail of viruses,鈥� in 2021.
But when Chin鈥檚 team made Syn61 available to other researchers, Nyerges and his colleagues, including George Church, exposed it to viruses from sources such as sewage, rivers and lakes. Twelve viruses were able to infect the strain.
This occurred because some viruses possess their own genes for tRNAs, which can compensate for the tRNAs deleted by Chin鈥檚 approach.
To combat this, Nyerges and his team modified Syn61 so the two freed-up codons that coded for serine now code for the amino acid leucine. This makes no difference to the bacterium because those two codons have been removed from its genes.
But when viruses infect this modified strain, their proteins have leucine added in places where there should be serine, rendering the viral proteins useless and preventing replication.
鈥淐onsidering the myriad of viruses out there, I don鈥檛 think it鈥檚 surprising that they found some capable of infecting Syn61 鈥� although I have to admit that until this preprint I didn鈥檛 realise viruses had this mechanism to avoid the missing tRNA problem,鈥� says at Imperial College London.
鈥淚 don鈥檛 think we can ever say it鈥檚 100 per cent foolproof, but I think the approach used in this preprint is very, very, very unlikely to be something that viruses can find a way around.鈥�
Nyerges鈥檚 team also made the modified strain dependent on an artificial amino acid to prevent it from spreading outside labs and factories.
Chin didn鈥檛 respond to questions from 快猫短视频.
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