There is a growing concern about the emergence of bacterial strains showing resistance to all classes of antibiotics. Today, in the US, more people are killed by Methicillin Resistant S. aureus than by AIDS. Though, there is no such report on crude infectious disease mortality rate in India, the absence of evidence is not evidence of absence. More so when India’s antibiotics consumption has increased by 103% between 2000
and 2015, leading to India having one of the highest rates of antibiotic resistance in the world.
Since the discovery of Penicillin, there have been warnings about overuse and non-medical use of antibiotics and the risk of microbial drug-resistance. In 2014, around seven lakh people across the world died due to infections associated with drug-resistance, a number that is estimated to touch 10 million by 2050. The global crisis of antibiotics resistance has thus come to a point at which if action is not taken, human medicine will enter a post-antibiotic world and simple injuries could once again become life-threatening.
‘Ganga Snan Thunga Paan’ — bathe in the Ganga, drink from the Thunga — is a widely held belief. The holy water of the Ganga is believed to be self-cleansing in nature. Therefore, bathing in the Ganga is believed to “wash away one’s sins” by killing regular infections. This was evidenced by English bacteriologist Ernest Hanbury Hankin in 1896, when he reported that the water of the Ganges kills the cholera germ in less than three hours. But the same water, when boiled, failed to do so, suggesting that something in the waters of the Ganga had marked antibacterial action against cholera, and it was one of the possible reasons for limiting the spread of cholera epidemics along its banks.
Later, these natural enemies of bacteria were identified as bactriolytic viruses and named as bacteriophage or phage. The healing powers of the Ganga are due to millions of bacteriophages in it that can parasitise and kill bacteria. Phages are incredibly abundant and omnipresent, found wherever bacteria exist -- in soil, in rivers that catch waste runoff from sewers, and in the stools of recovering patients.
The application of bacteriophages to treat bacterial infections has been around for almost a century, particularly in the former Soviet Union and Eastern Europe. However, the successful intervention of modern antibiotic therapy overshadowed the global applications of phage therapy. Currently, the healthcare system in both developed and developing countries are facing a major threat from multidrug-resistant pathogens.
It is the right time to adopt non-antibiotic antimicrobials as an alternative prophylactic approach to treating bacterial infections at the minimum for non-medical applications. For instance, the food industry, agricultural sectors, aquaculture and domestic uses can be thought of. This will minimise the rate of antibiotic production and usage — and therefore also antibiotic residues in the environment that leads to resistant bacteria.
Phage therapy is witnessing a well-deserved rebirth. As a result, for the first time, the US clinical trial of intravenously administered bacteriophage therapy received FDA approval to evaluate the safety and efficacy of an experimental bacteriophage therapy for patients with ventricular assist devices (VAD)-associated Staphylococcus aureus infections. Further, the FDA and the USDA also approved the PhageGuard-E, PhageGuard-S and PhageGuard Listex (the natural phages against E. coli O157, Salmonella and Listeria monocytogenes respectively) as a GRAS (Generally Recognised as Safe) for dairy and food processing products.
To make bacteriophages more potential and robust, researchers started exploring the phage lytic enzymes as antimicrobials. Many bacteriophages encode tail-spike proteins that bind to receptors on the bacterial surface. These bacteriolytic cell wall hydrolases (endolysins) degrade the peptidoglycan in the bacterial cell wall and act as potential antimicrobial agents.
Compared to antibiotics, these endolysins have three distinct features: (1) ability to target specific bacteria while preserving the microbiome which is essential for our health; (2) ability to kill multi-drug resistant strains of bacteria; (3) emergence of resistance against endolysins is not expected. In general, the classic antibiotics require hours to kill bacterial cells that are metabolically active, whereas the endolysins are spontaneous and fast-acting, destroy metabolically active and persistent bacterial cells in minutes.
This has boosted the study of these enzymes as new anti-microbials in different fields. As a result, Staphefekt SA.100 is the world’s first endolysin approved for human use. Staphefekt selectively targets S. aureus, including MRSA — which is a major trigger of eczema and other inflammatory skin conditions. It is currently registered as a (class 1) medical device in Europe and is available in a cetomacrogol-based cream and in a gel as over-the-counter treatment. There are other potential products under clinical trials.
India is the second largest country by population as well as by antibiotic consumption. It is time to dust-off this long-forgotten weapon — bacteriophage — to cope with multi-drug resistant pathogens. We should take the lead in adopting regulatory requirements to set up pharmaceutical and pre-clinical safety assessment for the therapeutic applications of bacteriophage and phage-derived enzymes.
(The writer is Senior Scientist, Ella Foundation, Genome Valley, Hyderabad)