Phage Renaissance: New Hope against Antibiotic Resistance

Abstract

In the 1920s and 1930s, before widespread use of anti-biotics, physicians successfully treated a variety of infections with bacteriophages, or phages for short. These natural viral predators, which target bacteria but leave mammalian and plant cells unscathed, were sold by pharmaceutical companies including Eli Lilly & Company1 and even made it into the fiction of the time—the protagonist of Sinclair Lewis’ 1925 book Arrowsmith fought bubonic plague with phages.2 Phages on the surface of an Escherichia coli cell inject genetic material into the bacterium. Scientists of the day did not understand exactly how phages killed bacteria, and their crude therapies performed inconsistently. So with the mass production of “magic bullet” antibiotics in the 1940s and 1950s, interest in phages largely waned.1 But 60 years later, antibiotics are losing their luster. Antibiotics have not only been used to treat human infections but also are given to farm animals to speed growth and prevent illness. They end up being flushed down drains and leach into soil and groundwater, where they contribute to environmental hot spots of antibiotic resistance.3 Antibiotic-resistant microbes now pose a growing threat to people of all ages, nationalities, and socioeconomic backgrounds, and previously treatable diseases are becoming untreatable once more.4 Researchers, too, are looking back to the pre-antibiotic era, but with the goal of resurrecting phages as antidotes for antibiotic resistance and solving medical, agricultural, and environmental problems. This time around, they are armed with molecular biology tools to better understand and control phages. They can also draw on the experience of Eastern European investigators, who have continued to study these viruses for decades, publishing their work primarily in Russian, Georgian, and Polish journals.1 In these countries, phages have continued to be given orally as tablets and liquids, topically, rectally, and as injections for 90 years. No reports of serious side effects have been recorded, and fever and other minor side effects came from contaminants like endotoxins in early phage preparations.1