January 25, 2016
In an effort to address the real and serious public health threat of antibiotic resistance, researchers from The Westmead Institute are taking a second look at an alternative therapy which has the potential to be our best defence against superbugs.
Misuse of existing antibiotics has led to rising resistance levels in bacteria causing serious disease. To combat the looming threat, researchers from the Westmead Institute’s Centre for Infectious Disease and Microbiology have been awarded a $867,716 NHMRC grant to investigate the eradication of high-risk bacterial infections using bacteria-killing viruses.
The use of bacteriophage, or phage therapy for short, is not new according to the Institute’s Dr Carola Venturini, who specialises in antibiotic resistance in gut bacteria. Discovered in the early 1900s by the English bacteriologist Frederick Twort and French-Canadian microbiologist Felix d’Herelle, phages were used to treat bacterial infections up until the 1920s.
“Although phage therapy was proving successful, it largely went out of use in Western countries with the advent of powerful antibiotics” says Dr Venturini. “Antibiotics were very effective, and nobody was thinking about antibiotic resistance back then.”
However, Dr Venturini says that while the West had left these bacteria-fighting viruses behind, phage therapy was flourishing in Russia.
“Behind the Iron Curtain there was a big push for phage therapy and they had a lot of success, particularly in burns patients and with skin infections. But because of the cold war, we didn’t really have access to real, solid research to back up this information.”
In the desperate war against antibiotic resistance, phage therapy is making a comeback, and Dr Venturini and her colleagues are at the forefront of this research in Australia.
“Phage therapy has really come to life in the last 5-10 years. The antibiotic pipeline is drying up - there is no real investment in antibiotics anymore because of the development of resistance,” says Dr Venturini.
“It is in the forefront of your mind. While you are investigating all of the molecular mechanisms for resistance you realise that, fundamentally, it is a race between us and the bacteria. And the bacteria are going to win.
“So people are turning to alternative ways of treating infection to curb the development of antibiotic resistance. Phage therapy is very appealing because you are exploiting an interaction between the bacteria and their natural predators.”
The project at the Westmead Institute examines a potential role for phage therapy in eliminating bacteria responsible for antibiotic-resistant gut infections. These superbugs pose worldwide public health risks, with periodic outbreaks emerging in all our major cities.
“We are looking specifically at bacteria that cause sepsis – E. coli and Klebsiella - directly in intensive care patients. These bacteria can spread easily through travel, are multiply resistant and are becoming a big problem worldwide. We need to be smart and preempt any large outbreak.”
This is not the first time researchers from the Westmead Institute have investigated the use of phage therapy. In 2010, Professor Jon Iredell, who heads the Institute’s Critical Infection Group and is the Director of Infectious Diseases at the Westmead Hospital, used adjunctive phage therapy to successfully treat a 67-year-old woman who was suffering from an antibiotic resistant urinary tract infection. As well as a microbiological cure, the patient experienced no side effects from the treatment, which was found to be self-limiting.
The wonder of phage therapy, says Dr Venturini, is that it is target specific, and therefore safe.
“Phage is a beautiful thing. They don’t invade mammalian cells, they don’t do anything to your blood cells – they just go and hit the bacteria. And while there is still a risk of developing resistance, it can be circumvented more easily than with antibiotics.”
But the targeted nature of bacteriophages is a double-edged sword.
“The trick is to be able to isolate the right phage for the right bacterium. Our research is important in terms of developing a protocol for the isolation of specific phages against very specific set of strains. Ultimately, we would like to develop diagnostic methods for quickly and accurately predicting bacteriophage susceptibility, so that we can choose the right phages in the same way we choose the right antibiotics.
“Furthermore, if our protocol for putting together the cocktail of phages works, it can be applied to other infections in plants and animals.”
Ironically, says Dr Venturini, one of the big hurdles of phage therapy has nothing to do with science.
“Regulation is a challenge. Because phages are natural, they are not considered a drug and the regulations should be quite easy. But in actual fact, it makes it more complicated because the regulatory framework isn’t in place yet. Currently phage therapy is only approved for use in extreme cases, for example with immune-compromised patients with chronic infections.”
“We know it works. It is just a case of how we can effectively use it therapeutically. Our research is about building a framework that can work in therapy.”