Bacteria armed with a CRISPR-based weapon that infects other microbes during the bacterial equivalent of sex could help us kill off dangerous antibiotic-resistant superbugs 鈥� if regulators approve their use. While the approach has huge promise, its reliance on genetically engineered bacteria is likely to be controversial.
鈥淲e would be releasing genetically modified killing machines into the environment. What could go wrong?鈥� says David Edgell at Western University in Canada.
There are two main problems with conventional antibiotic drugs. First, they often kill beneficial bacteria along with dangerous ones and disrupt microbiomes. This is why a dose of antibiotics can trigger diarrhoea.
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Second, many bacteria are becoming resistant to the drugs, including antibiotics such as carbapenem that are regarded as one of the last lines of defence.
In theory, the CRISPR gene-editing technique can solve both problems. It can be adapted to kill harmful bacteria by targeting specific DNA sequences, while leaving bacteria that lack these sequences unharmed.
The main obstacle is getting DNA coding for the necessary CRISPR machinery inside bacterial cells. One way to do this is to exploit the bacterial equivalent of sex, a process called conjugation during which two bacteria link up via a narrow tube and transfer circular pieces of DNA known as plasmids. Antibiotic resistance often spreads on plasmids.
Guillaume Launay at the University of Lyon, France, and his colleagues did this by creating a plasmid coding for the CRISPR machinery needed to target the genes for carbapenem resistance. They then added this targeted antibacterial plasmid to a strain of E. coli bacteria.
Finally, they mixed the engineered E. coli with other bacteria, including some that were resistant to carbapenem. As they hoped, the carbapenem-resistant bacteria were eliminated from the mix.
This approach could be used to prevent infections by antibiotic-resistant superbugs, as well as to treat them. 鈥淚t could serve as a preventive means to reduce the amount of resistant bacteria in the gut, for example,鈥� says Matti Jalasvuori at the University of Jyv盲skyl盲 in Finland. 鈥淭his could lead to fewer resistant bacterial infections in patients that are at risk.鈥�
Edgell鈥檚 team has . It could also be used to tweak the microbiomes in our guts and on our skin in beneficial ways, he says, such as by eliminating species associated with acne.
However, it is possible that regulators will approve such treatments only if the bacteria carrying the CRISPR plasmids, or the plasmids themselves, can be prevented from spreading in the wider environment.
The bacteria initially equipped with CRISPR plasmids are unlikely to become a permanent part of microbiomes, says Edgell. However, the plasmids they carry will be transferred to non-target bacteria as well as target bacteria and could persist indefinitely. That could be regarded as a good thing because they will continue to kill the target bacteria as long as they are present.
Nevertheless, Edgell鈥檚 team is working on various containment methods, such as creating plasmids that self-destruct if they are in an environment below human body temperature. 鈥淧ublic and regulatory approval will be critical,鈥� he says, but he believes it will be forthcoming. 鈥淚 think it is inevitable that modified bacteria will be used in clinical or therapeutic settings.鈥�
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