Hervé Le Moual, Jenny-Lee Thomassin and John R Brannon
The spread of antibiotic resistance genes amongst microbes, the emergence of multi-drug resistant bacterial pathogens and the paucity of antibiotics in development have caused a major health care crisis. With few options available to treat multi-drug resistant bacteria, it is critical to develop alternative therapies to conventional antibiotics. An auspicious alternative strategy stems from antimicrobial peptides (AMPs), which are the host’s own “endogenous antibiotics”. AMPs are produced at mucosal surfaces, where they exert both bactericidal and immunomodulatory activities making them important components of the innate immune system. To date, the development of AMPbased therapies has focused on developing synthetic peptides with tailored activity and boosting endogenous AMP-expression. These therapies may be confounded by the multiple bacterial AMP-resistance mechanisms that have arisen during the co-evolution of bacteria with their hosts’ innate immune system. Therefore, approaches that counteract bacterial AMP-resistance mechanisms can be added to the arsenal of novel therapies. This review provides an overview of human AMPs and summarizes the current strategies used to develop AMP-based therapies with particular focus on a novel strategy that aims to boost AMP activity by inhibiting bacterial AMP-resistance mechanisms.