A new research led by Dr Kimberley Seed from the Tufts University School of Medicine provides the first evidence that bacteriophages – viruses that infect and replicate within bacteria – can acquire a wholly functional and adaptive immune system.
The study, published today in the journal Nature, finds that a viral predator of the cholera bacteria can steal the functional immune system of bacteria and use it against its bacterial host. The bacteriophage (phage for short) used the stolen immune system to disable – and thus overcome – the cholera bacteria’s defense system against phages. Therefore, the phage can kill the cholera bacteria and multiply to produce more phage offspring, which can then kill more cholera bacteria.
The discovery has dramatic implications for phage therapy, which is the use of phages to treat bacterial diseases. Developing phage therapy is particularly important because some bacteria, called superbugs, are resistant to most or all current antibiotics.
Until now, scientists thought phages existed only as primitive particles of DNA or RNA and therefore lacked the sophistication of an adaptive immune system, which is a system that can respond rapidly to a nearly infinite variety of new challenges. Phages are viruses that prey exclusively on bacteria and each phage is parasitically mated to a specific type of bacteria. This study focused on a phage that attacks Vibrio cholerae, the bacterium responsible for cholera epidemics in humans.
The researchers used phage lacking the adaptive immune system to infect a new strain of cholera bacteria that is naturally resistant to the phage. The phage was unable to adapt to and kill the cholera strain. They next infected the same strain of cholera bacteria with phage harboring the immune system, and observed that the phage rapidly adapted and thus gained the ability to kill the cholera bacteria. This work demonstrates that the immune system harbored by the phage is fully functional and adaptive.
“Virtually all bacteria can be infected by phages. About half of the world’s known bacteria have this adaptive immune system, called CRISPR/Cas, which is used primarily to provide immunity against phages. Although this immune system was commandeered by the phage, its origin remains unknown because the cholera bacterium itself currently lacks this system. What is really remarkable is that the immune system is being used by the phage to adapt to and overcome the defense systems of the cholera bacteria. Finding a CRISPR/Cas system in a phage shows that there is gene flow between the phage and bacteria even for something as large and complex as the genes for an adaptive immune system,” Dr Seed said.
“The study lends credence to the controversial idea that viruses are living creatures, and bolsters the possibility of using phage therapy to treat bacterial infections, especially those that are resistant to antibiotic treatment,” added senior author Prof Andrew Camilli, also from the Tufts University School of Medicine.
Bibliographic information: Seed KD et al. 2013. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nature, vol. 494, no. 7438, pp. 489–491; doi: 10.1038/nature11927