Next generation of “magic bullets”, solutions from the microbial pangenome

Identification of a toxic agent that—like a sniper—would be capable of targeting pathogenic bacteria and effectively discriminating between “good” and “evil” cells has long been the holy grail of drug discovery. The theory of magic bullet, first pioneered by Paul Ehrlich in the early 1900, has represented since then a “ leit motif” in immunological research against infectious diseases. Salvarsan, the first arsenic-based drug against syphilis, was the first example showing that this concept was in fact a realistic goal. Later, a paradigm shift took place with pathogenic bacteria becoming the source of the magic bullets (i.e., the toxins), and tumorigenic cells the enemy to combat; thus paving the way to immunotoxins discovery and development. In this issue of EMBO Molecular Medicine , Gill et al, describe a new toxin platform for cancer therapy (Gill et al, 2024 ). V. Masignani, R. Rappuoli, and M. Pizza discuss the study from Gill et al, published in this issue of EMBO Mol Med , that describes a new toxin platform for cancer therapy.