LAUSR

The bleakest outlook for a “post-antibiotic era” is one in which microbial infections can no longer be cured. The traditional antibiotic pipeline has been exhausted, while antimicrobial resistance has become a multifaceted crisis, imposing a serious threat to human health with more than 700,000 deaths each year globally. Furthermore, in line with the latest reports from the World Health Organisation (WHO), this number is expected to grow up to 10-fold by 2050, meaning that infectious diseases will be the principal cause of mortality rather than cancer (Sulis et al., 2021). The growing ineffectiveness of clinically used antibiotics could result in new pandemics that will be difficult to stem without effective replacement drugs. The current SARS-CoV-2 crisis is illuminating with respect to the consequences of being poorly armed to combat infection, and how this impacts all aspects of modern society; medical, social, and economic. From this scenario, it is clear how the discovery of new antimicrobial treatments is highly demanded. Inspired by nature, antimicrobial peptides (AMPs) and secondary metabolites (SM) are gaining attention for their clinical translation and remain the best storehouse for leads in modern drug discovery. AMPs are evolutionarily conserved elements of the innate immune system of almost all living organisms and have distinct advantages compared to conventional antibiotics. Indeed, they have a large spectrum of antimicrobial activity and cause cell disruption through a non-specific mechanism based on the perturbation of the target microbial cell membrane, thus making microbes less prone to acquire resistance to them (Sarkar et al., 2021). AMPs also display additional functions that indirectly promote the clearance of microorganisms through the modulation of inflammatory host responses and the promotion of wound healing. In addition, some of them have promising anticancer properties. However, some inherent drawbacks of AMPs need to be overcome for their clinical translation. Among them, the short half-life owing to the susceptibility to protease degradation; the inactivity at physiological salt concentrations; the cytotoxicity towards host cells, and the limited targeted delivery. Currently, most of the AMPs under clinical evaluation are positively charged derivatives of naturally occurring AMPs and are limited to topical administration for an effective concentration at the target site (Casciaro et al., 2017). Edited and reviewed by: John D. Wade, University of Melbourne, Australia