Oct 07, 2024 08:56 PM IST
Bacteriophages, or simply, “phages”, have potential not only to fight drug-resistant bacteria, but also to lower resistance in them. For a country that is staring at a serious drug resistance problem, phage therapy could be a way out
Hollywood seems to have an uncanny knack for picking both villains and heroes from the large cast of viruses in our environment. Steven Soderbergh’s Contagion (2011) was about a pandemic caused by the fictional MEV-1 virus (derived from a combination of respiratory viruses that infect pigs and bats). In retrospect, the film becomes an eerie premonition of Covid-19, which was, of course, driven by the villainous SARS-CoV-2 virus. We may see a heroic “phage” virus in a movie that is being made on the real-life story of San Diego-based epidemiologist Steffanie Strathdee. She acquired global fame for saving her husband’s life by using bacteria-fighting viruses as he lay critically ill.
Steffanie’s husband, Patrick, was infected by Acinetobacter baumannii while travelling in Egypt in 2015. Powerful antibiotics failed to cure the life-threatening, multi-drug resistant abdominal abscess caused by this superbug that tops the World Health Organization’s list of dangerous bacteria. Strathdee desperately scoured scientific literature and found a study from Tbilisi, Georgia, which reported the successful use of bacteria-destroying viruses (bacteriophages). With help from the Food and Drug Administration (FDA) of the United States, she obtained a phage cocktail from a laboratory in Georgia and also from a naval research centre working on oceanic microbes. Patrick’s recovery resulted in the book The Perfect Predator. This determined scientist’s triumphant rescue of her spouse has a movie in the making.
Bacteriophages (usually referred to simply as phages) are viruses that invade bacteria and seize their genetic material to make copies of themselves. The resulting brood escapes from the bacterium by destroying it. Such viruses are ubiquitous and can even be isolated from wastewater containing human excreta. The human gut contains a large collection of viruses (the phageome), which balances the bacterial microbiome by killing the bad bacteria and allowing good bacteria to thrive. As efficient gene-delivery agents, phages also help bacteria by bringing them new genes. The amazing ingenuity of nature, in this balancing of contending forces in the microbial world, protects us from harm. Across our natural world, phage predation is estimated to destroy one-half of the world’s bacteria every 48 hours!
The lower the diversity of the phageome in our bodies, the greater the risk of diseases like inflammatory bowel disease and colorectal cancer. That said, there are good phages and bad phages. High levels of diversity assure the dominance of good phages. Like the microbiome, phage population is responsive to environmental factors like the composition of our diet, drinking water quality, tobacco and alcohol consumption.
In 1896, Ernest Hankin discovered that a lytic cocktail produced by viruses could destroy cholera-causing bacteria. Felix d’Herelle first developed phage therapy, in 1919, to stop a typhoid outbreak in chickens. Initially, scientists were willing to use this microbial intervention only in animals. Human use followed after some delay when phage therapy was found useful for septic wounds. When western nations started using newly developed antibiotics in the 1940s, they lost interest in phages. However, the erstwhile Soviet Union and East European countries continued to develop and use phage therapies, as they did not have access to antibiotics produced in the West. Their phage libraries are now attracting global interest.
The value of phage therapy was demonstrated when antibiotics failed to control bacterial infections. In 1961, when actress Elizabeth Taylor was in London for the filming of Cleopatra, she fell ill with severe staphylococcal pneumonia and underwent a tracheostomy — a surgical creation of an opening in the neck to function as an airway and facilitate breathing. A staphylococcal phage lysate, prepared in a Philadelphia laboratory, was flown to London. Taylor received this treatment, recovered, and as is known now, Cleopatra went on to win four Oscars. In recent years, phage therapy has been found very useful for treating clostridium difficile infection of the colon, an extremely serious condition that occurs when the integrity of the colon’s mucosal lining is damaged by extensive use of antibiotics. Recently, scientists at Liverpool and Yale reported that viruses can even reverse antibiotic resistance among bacteria.
Pseudomonas aeruginosa causes life-threatening infections. It is often hospital-acquired and is resistant to many antibiotics. The bacterium uses four efflux pumps on its surface to pump out antibiotics before they attain lethal concentrations within its body. Phages enter through those pumps, leaving the bacterium a choice between fighting the deadly intruder at the gates or using them to pump out the drug. For immediate survival, the bacterium chooses to battle the phage and shuts the door on it. The antibiotic accumulates in the bacterial cell and kills it. Phages also inactivate the gene that forms the bacterial cell membrane. Surely, even cinema cannot script a thriller better than this!
Phages abound in places where bacteria grow — wastewater, garbage, bilge, human and animal excreta. Many countries are now actively hunting for phages, hoping to counter antimicrobial resistance, which is predicted to kill 40 million persons by 2050. India, too, must use its scientific agencies and research institutions to search for friendly phages amidst its vast natural resources of land and water. They can be our saviours against the onslaught of drug-resistant bacteria. The Bhabha Atomic Research Centre (BARC) has taken the lead in this area. Our regulatory systems will have to be prepared to review and accept these new forms of therapy. Currently, many countries are permitting phage therapies on compassionate grounds for very sick patients. As scientific evidence accumulates on the efficacy and safety of phage therapies, clear guidelines will emerge to permit their use. Till then, we follow this cinematic story as it unfolds, with edge-of-the-seat anticipation.
K Srinath Reddy is distinguished professor of public health, PHFI, and the author of Pulse to Planet.The views expressed are personal
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