Expanding the Antimicrobial Toolbox with Therapeutic Viruses: Mechanisms, Pharmaceutical Formulation, and Translational Outlook.

Infectious diseases continue to represent one of the most persistent challenges in human health and agricultural productivity. These diseases are caused by a wide range of pathogenic microorganisms, including bacteria, fungi, viruses, and parasites. Antimicrobial resistance, or AMR, is the gradual evolution of pathogenic microbes to evade the action of commonly used antimicrobial agents (antibiotics, antifungals, antivirals, and antiparasitics) and is a problem that continues to be exacerbated by the inappropriate use of antimicrobials across multiple global industries. AMR poses a major threat to our society, and without mitigation, will lead to devastating consequences with broad implications beyond human health. The search for alternative or complementary therapies to conventional antimicrobials is, therefore, of the utmost priority. In this review, we first outline the prevalence of AMR and the circumstances driving the proliferation of AMR, which is widely recognised as a One Health issue-through interconnected factors within human and veterinary medicine, agricultural practice, and the environment. We next summarise the various classes of pathogens, common antimicrobial agents, and the mechanisms which pathogens have evolved to evade antimicrobial action. Within this context, we discuss the therapeutic potential of bacteriophages, virophages, and mycoviruses against antimicrobial-resistant infections, and consider the future perspectives of virus-based formulations.