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European Biopharmaceutical Review

A New Generation of Agents Combatting Antibiotic Resistance

In recent decades, extensive use of antibiotics in medicine, the meat industry, and agriculture has led to the emergence and dissemination of antibioticresistant bacteria. This has in turn contributed to the rise of nosocomial multi drug resistant (MDR) bacterial infections, which are now posing a huge burden on the healthcare system worldwide. The concept of antibacterial resistance is not new, given that many bacteria share the same environmental niche with other microbes and have developed defence systems to combat each other. What drives the clinically detrimental spread of MDR bacteria is the widespread use of antibiotics by humans alongside the relentless environmental battle between microorganisms. Commercial antibiotic development is having difficulty keeping up with the rise in antibiotic resistance – next-generation versions of chronically used antibiotics, designed to overcome or evade existing resistance mechanisms, are increasingly falling victim to the evolving prevalence of resistance. The challenges to developing effective antibiotics include the length and high cost of the discovery and development process, together with safety, efficacy, and manufacturing risks – all exacerbated by an accompanying detrimental effect on the gut’s native microbiota due to broad-spectrum antibiotic activity. Therefore, identifying novel, selective, and cost-effective antibacterial agents is of utmost importance.

Phages vs Antibiotic-Resistant Bacteria

Bacteriophages (phages) have long been considered as natural antibacterial agents and have been used therapeutically for over 100 years (1). While the study of therapeutic phages has long been overshadowed by the discovery of antibiotics, rapidly emerging antibacterial resistance has brought them back into the spotlight. Phages are abundant in nature with an estimated 1031 virions on the planet, making them easy to identify and isolate (1). As pervasive, obligate bacterial parasites, phages are extremely successful in targeting specific bacterial hosts, replicating, and ultimately releasing progeny by inducing cell lysis, all while circumventing antibiotic resistance mechanisms. In contrast to antibiotics, many phages are capable of infecting and destroying bacterial biofilms (2-3). Naturally occurring, or wild-type (WT) phages are already being exploited for their therapeutic potential. However, the rise in advanced computational, genetic, and molecular tools has galvanised interest in phage biology and phage engineering, which dramatically increases opportunities for their therapeutic utility.

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Dr Heather Fairhead is founder and CEO of Phico Therapeutics, a biotech company developing a novel antibacterial technology called SASPject. Prior to starting Phico, she worked as a researcher at the University of Connecticut Medical School, US, and the University of Cambridge, UK, and developed a small research lab for a Cambridge startup. Heather has a BSc (first) in Biotechnology from the University of Nottingham, UK, and a PhD from the University of Sheffield in Molecular Microbiology.
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Dr Heather Fairhead
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