University of Sydney: Natural virus predators offer potential alternative to antibiotics

Researchers at the University of Sydney, Western Sydney Local Health District and the Westmead Institute for Medical Research are developing a therapeutic solution to antimicrobial resistance that predates the discovery and wide usage of antibiotics.

Professor Jon Iredell from the Faculty of Medicine and Health and his team at Phage Australia, are harnessing the natural virus predators of bacteria, called bacteriophages or phages that are found everywhere in nature. In fact, they are the most abundant and diverse life form on Earth.
By the year 2050, antimicrobial resistance is predicted to become the leading cause of death globally, taking an estimated 10 million lives per year and exceeding deaths from cancer and cardiovascular disease.

The World Health Organisation has warned that the failure of antibiotics due to antimicrobial resistance could lead to an end to modern medicine as common infections become untreatable and surgical procedures carry an increased risk of infection, sepsis and mortality.

According to Professor Iredell, the Asia-Pacific region will be particularly impacted by antimicrobial resistance with the estimated annual impact on the global economy by 2050 expected to be between $100 and $120 billion.

Phage therapy was first used a century ago and continues to be a popular treatment option for bacterial infection in Eastern Europe, but it fell from favour in the West after the discovery of antibiotics.

“Phages attack and effectively fight and destroy multi-drug resistant bacteria, making them a suitable alternative to antibiotics for treating bacterial infections,” said Professor Iredell.

“With careful preparation to remove impurities, phages are harmless to humans, easy to produce and completely effective against antibiotic-resistant bacterial strains – offering a last defence against otherwise untreatable infections.”

Currently, Phage Australia can only provide phage therapy in compassionate cases. Following successful studies on severe sepsis at Westmead Hospital, infection specialist at the Children’s Hospital, Westmead and Deputy Director of Phage Australia, Dr Ameneh Khatami, said she recently helped doctors successfully treat a life-threatening lung infection and save the leg of a seven-year-old-girl facing amputation as a result of an ongoing antimicrobial-resistant infection.

The team now wants to make the therapy widely available across the Australian health system by establishing it in the Australian (and international) pharmacopeia through a national industry ecosystem of genomics and informatics, diagnostics, clinical trials, manufacturing and international biobanks.

The researchers have already assembled a leadership team, begun production of phages, enrolled their first patients in clinical trials and are developing infrastructure for implementation and analysis.

Over the next five years, they aim to deliver precision phage therapy to Australians and define its role for prescribers and patients across the Asia Pacific region. They will also work with regulators to find a place for phage therapy in the national pharmacopoeia – established standards for pharmaceutical substances and medicinal products which assist in the quality control of medicines in Australia. At this stage, therapy is not TGA approved.

One of the big advantages of phage therapy is its ability to precisely target strains of bacteria. Unlike antibiotics, each phage is highly precise in the specific bacteria it targets. This means that, unlike broad-spectrum antibiotics, phage treatment does not impact the healthy bacteria in the human body, making it a suitable third approach to infectious disease control (after immunisation and antibiotics).

According to Deputy Director of Phage Australia, Associate Professor Ruby Lin this specificity is what makes phage therapy so important for the future of public health.

“Phage can be a powerful treatment weapon for clinicians because it is so targeted. You can specify how much load you want to release into the site of infection, dictating exactly how many milligrams, or nanograms of drugs you want to deliver,” she said.

Associate Professor Lin believes that the development of phage therapy also has the potential to prepare the Australian health system for future outbreaks of infectious disease.

“When COVID-19 happened, we weren’t ready to deal with infectious diseases. Medical countermeasure is very important, and phage therapy is part of that overall picture of surveillance and preparedness for a pandemic and antimicrobial resistance,” she said.

“We still need antibiotics, but phage therapy can offer another solution. Ideally, we would like to add phage therapy to the Australian pharmacopeia. There is a global movement toward phage therapy as it is the only way to deal with antimicrobial resistance.”

Professor Iredell and his team at Sydney are researching genomic technologies that will help evolve phage into a better weapon to fight infection.

“We pioneered phage therapy for humans in Australia in 2007 and are still the only site in Australia who have treated adults and children with phage therapy,” he said.

“The momentum we have created is very strong, but we cannot maintain our leadership position without funding support, this is very urgent now.”

Professor Iredell is hoping that Phage Australia will receive the funding needed to deliver the Southern Hemisphere’s first sustainable source of phage therapy.