Unexploited opportunities for phage therapy

(2015) Unexploited opportunities for phage therapy. A Surprising Twist on Bacteriophage Therapy Bacterial infections have always been a threat to human health. The first available systemic antibiotics, in early twentieth century, were initially seen as truly miraculous drugs, providing a powerful tool to combat bacterial infections and increasing human life span. Deluded by their exceptional antimicrobial properties, they quickly fell in trivial use to fight even the most common types of infections, many of non-bacterial nature. This indiscriminate use of antibiotics allowed bacteria to develop defense systems to become less prone to antibiotics-multiresistant-superbugs, a development that Sir Alexander Fleming already anticipated when he gave his Nobel lecture in 1945. Bacteriophages (phages) are natural predators of bacteria that specifically parasite bacteria to replicate, and were discovered in the early part of the twentieth century, independently by Twort (1915) and d'Herelle (1917) (Summers, 2005). The ability to kill bacteria was soon therapeutically explored by d'Hérelle and his followers while fighting various bacterial infections around the world, such as the bubonic plague in Southeast Asia, dysentery in France, and cholera in India. Phage therapy was extensively used to treat infectious diseases during World War II too (Summers, 2001). However, insufficient knowledge of phage biology, low quality control of phage preparations and lack of solid scientific evidence of therapeutic successes led to phage failure over the newly discovered antibiotics till the second half of the twentieth century. The alarming emergence of antibiotic resistant bacteria is considered the greatest threat to human health of the new millennium by both the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in addition to many other health-caring organizations worldwide (El-Tahawy, 2004; Rice, 2009). With this new reality, scientific community and business players have revived their interest in phages as an alternative therapy. The ability of phages to kill antibiotic-resistant bacteria allied with their ubiquitous nature, high specificity (minimal disruption of normal flora), prevalence in human gastrointestinal tract, self-replication ability at the infection site, and low inherent toxicity qualifies them probably as the most " safe " and " green " technology available for clinical application. Several studies are currently providing convincing evidence regarding the safety and efficiency of phage therapy in animals and humans (Sulakvelidze et al., 2001; Sillankorva et al., 2012), with recent appearances of new phage companies and commercial phage-based products (Thiel, 2004; Housby and Mann, 2009). …