By: Anza Abbas
Bacteriophage also known as a phage is a virus that acts like a sinister alien and infects bacteria. The structure of phages consists of genetic material encapsulated in a protein coat. Viruses inject only genetic material and hijack the bacterial cell during infection. The bacterial cell will act like a phage factory and virus particles are released at the end of the lytic cycle causing cell death. They are widely spread on earth and infect bacteria with great specificity. Félix d’Herelle acknowledged the use of a technique called phage therapy (treatment of bacterial infections with phages) in 1917. Soon it was replaced with antibiotics which can kill a wide variety of bacteria. Misuse of antibiotics in human, veterinary, agriculture, and industrial sectors led to the development of antibiotic-resistant bacteria. According to the U.S Centers for Disease Control and Prevention (CDC), antibiotic‐resistant pathogens cause more than 2 million illnesses and at least 23,000 deaths each year. Therefore, scientists are searching for alternative treatments and phage therapy has proved as a promising tool.
Phage therapy is considered the best alternative treatment due to the number of advantages and minimum side effects. Phages show a phenomenon called autodosing in which they determine their dose according to the host present. They will be automatically wiped out when hosts have been lysed. To broaden their range, phage cocktails (a combination of two or more phage types) can be used against multidrug-resistant bacterial diseases. They can also be combined with antibiotics for developing therapies. Most importantly, phages can overcome resistant strains by evolving themselves. To this end, preclinical studies of phage therapy have suggested a 100% success rate against multidrug-resistant pathogens.
Phages have adapted various phenomena to affect targets efficiently. Like, receptorbinding protein of phages can be modified to combat changes in bacterial cell surface receptors enabling phage adsorption onto a host cell. Some bacteria may produce exopolysaccharide biofilm or a capsule around the cell preventing phage binding. But phages can mask its effect by producing biofilm-degrading enzymes. Bacteria also possess a system called clustered regularly interspaced short palindromic repeats (CRISPR) along with Cas (CRISPR‐associated) genes to provide protection against foreign DNA or plasmids. However, phages have evolved and developed anti‐CRISPR systems to deliver their genome into host bacterial cells.
Different phage therapy approaches can be used to prevent bacterial infections. Such as the use of broad-spectrum phage cocktails (one-size-fits-all approach) can kill the majority of bacteria involved in the development of certain infectious diseases. Recently, several studies reported the success of phage cocktails against bacterial infections. For example, the number of Pseudomonas aeruginosa decreased in burn wounds due to susceptibility to the phage cocktail. Furthermore, BBC news reported on 8 May 2019 that viral cocktail saved a patient’s life. This remarkable study was published in the journal Nature Medicine explaining the whole story of phage use. Three-phage cocktail was used to treat Mycobacterium abscessus infection in a cystic fibrosis patient after bilateral lung transplantation. Two out of three phages were developed by genome engineering to make them more effective. Prof Martha Clokie, a phage researcher at the University of Leicester shed light on the significance of phage therapy. He highlighted the use of bacteriophages as therapeutics when bacteria get resistant to antibiotics.
Surprisingly, various studies have reported the efficacy of combined phage and antibiotic treatment. Oechslin et al. (2017) observed that phage in combination with ciprofloxacin showed a synergistic effect to lower the bacterial load to a great extent while treating endocarditis due to P. aeruginosa. Moreover, the Nobel Prize in Chemistry for 2018 was awarded to Greg Winter for contributions in phage display technique. This technique was first described by George P. Smith in 1985 in which a phage capsid is decorated with peptides or proteins. Different kinds of vaccines, genes, or drugs can be delivered by phage display. Some other applications include nanomaterials design, bioimaging, cancer research, and therapy.
Though phage therapy provides the opportunity to replace antibiotics, researchers have explored its potential in other applications such as gene transfer, bacterial biosensing, nanocarriers of vaccines and drugs, and many more. In the era of synthetic biology, modified phages can be used as effective antitumor nanomedicine. Phage‐based vaccines are found effective because they can act as nanodelivery vehicles or adjuvants for less immunogenic vaccines. The antiviral potential of phages suggests that phage‐based vaccines can also be used against different variants of SARS-CoV-2. This shows how the enemy’s (bacteria) enemy (virus) can act as a friend to humans.
The writer is student at NUST, Islamabad. She can be reached at [email protected]