A man with a very serious infection caused by antibiotic-resistant Escherichia coli has improved after being given bacteria-killing phage viruses armed with DNA-destroying CRISPR systems.
The infection developed in the months after the 65-year-old man had a kidney transplant. It led to a large mass growing on his bladder and large open wounds forming on his abdomen.
Conventional treatments, including antibiotics, failed to clear the infection, so the man鈥檚 doctors in California asked if they could try an experimental phage treatment developed by a Denmark-based company called SNIPR.
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Within a week of starting the treatment, the open wounds began to heal and the mass halved in size, from a volume of 0.74 litres to 0.37 litres.
The man was put on a new cocktail of more powerful antibiotics and other drugs 11 days before starting the phage therapy, so it is unclear whether the latter alone was the key. 鈥淚t could be that the phages together with the antibiotics had this synergistic effect,鈥� says Eric van der Helm at , one of the authors of a paper describing the case.
Bacteria can form thick biofilms that are difficult for antibiotics to penetrate, but previous studies by SNIPR have shown . So by breaking up biofilms, the phage may have made the antibiotics more effective, says van der Helm. 鈥淏ut we didn鈥檛 test that.鈥�
Bacteria-targeting viruses are extremely common. In fact, bacteriophages are thought to be by a huge margin. They are now widely used on food to kill bacteria that can cause food poisoning, but their use to treat bacterial infections remains rare, in part because of the time and expense involved in isolating phages that can kill the specific bacterium causing an infection.
But a number of companies around the world hope to change that. They are engineering phages to make them more powerful, by equipping them with CRISPR systems. CRISPR is best known for its use as a gene-editing tool but it evolved in bacteria as a defence against viruses, allowing bacteria to target and destroy specific DNA sequences in phages. Now, biologists have turned the tables, equipping the viruses with CRISPR systems that chew up specific pieces of bacterial DNA.
SNIPR鈥檚 initial plan was to specifically target E. coli that are resistant to antibiotics, says van der Helm. 鈥淏ut then we realised any E. coli is a problem once it enters the bloodstream.鈥�
So the company developed a cocktail of engineered phages known as SNIPR001 that is more potent than wildtype phages, and can kill 90 per cent of all E. coli strains. This treatment can be given orally to target E. coli in the gut, intravenously or applied directly to infected wounds.
Some cancer treatments increase the risk of E. coli-caused blood infections. A phase II trial is now under way in the US to see if lowering E. coli levels in the gut with SNIPR001 reduces the risk of such infections.
In the US, doctors can request the use of experimental treatments on a 鈥渃ompassionate use鈥� basis, as happened in the case of the 65-year-old man, who was given SNIPR001 intravenously and directly to his wounds.
No firm conclusions can be drawn from a single case, says van der Helm. 鈥淭hat鈥檚 why we鈥檙e keen to explore this in further in clinical trials.鈥� In the meantime, SNIPR has already had another 12 requests for compassionate use.
Clinical Infectious Diseases
