Warwick researchers discover giant phage with potential as a treatment for lung infections

Scientists have found a new bacteria-fighting agent that can attack a common lung infection caused by Burkholderia bacteria. This discovery has promising possibilities for use in biotechnology.

A family of bacteria known as Burkholderia cepacia complex can lead to lung infections, which can be lethal in people with severe lung conditions, especially cystic fibrosis. Burkholderia cenocepacia infections are challenging to cure because the bacterium may pump antibiotics back out of the bacterial cell or hide inside human cells.

Researchers from the University of Warwick's Sagona lab in the United Kingdom were keen to develop a means of concentrating on these elusive microorganisms. Researchers are increasingly exploring the use of bacteriophages (phages) as a method.

Naturally occurring viruses called phages are capable of infecting and killing bacteria. Although phages outnumber bacteria, animals, and people combined, they are still only sometimes employed as clinical therapies in the UK.

Finding a phage that can specifically target and eradicate B. cenocepacia was the first task for researchers, who hoped to provide alternative treatments for infected patients. Phages that target particular bacteria are abundant in wastewater, especially from hospitals. Scientists can isolate phages that can infect and kill Burkholderia if these bacteria are present in wastewater due to human bacterial input.

Using wastewater samples from a sewage treatment plant outside of Coventry, UK, Dr. Jessica Lewis, the study's investigator, first discovered a phage unique to B. cenocepacia. When evaluated, the phage not only eliminated B. cenocepacia but also showed that it is a jumbo phage.

A jumbo phage possesses a genome that is over twice the size of an average phage. These are rare—only a few hundred jumbo phages have been identified since the first one was isolated in 1978.

The discovery of a jumbo phage is especially thrilling because of the potential hidden within its genome. In the new phage, over 400 genes, making up around 85% of its total genes, have unknown functions. Dr. Lewis and her team are currently sequencing the DNA of this jumbo phage to uncover potential genes with novel and powerful functions.

Phage therapy with regular phage is step A, but if we do not want a repeat of resistance and similar problems that we face with antibiotics, we will need to optimize them.”

Dr. Jessica Lewis, Study Investigator, University of Warwick

By decoding the giant phage genome, Dr. Lewis and her colleagues intend to uncover DNA that can be modified to carry additional biological weapons, so expanding the phage's toolkit for identifying and eliminating B. cenocepacia.

Although much more research is required to move phages toward human and therapeutic uses, UK policy also places restrictions on researchers.

Currently in the UK, we cannot make our own phage therapeutics. We would have to isolate the phages here and send these off to certified phage companies either in mainland Europe or America so that they can generate purified phage cocktails (which are approved for phage therapy and can be applied to patients) and send those back to us.”

Dr. Jessica Lewis, Study Investigator, University of Warwick

Notwithstanding these obstacles, Dr. Lewis and her colleagues are going forward with their efforts to employ phage to specifically target B. cenocepacia, with the aim that their work will add to the abundance of phage research that will eventually be applied to patient care.

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