Is it justified to start talking about a "post-antibiotic period" in view of the threat of long-term loss of activity of these precious molecules, particularly if the discovery of new bactericidal molecules continues to stagnate? What are the options?
Anti-virulence molecules, vaccines and passive immunization, phagotherapy, stimulation of innate immune defenses, killer bacteria such as Bdellovibrio: even when revisited in the light of modern biology, these approaches may offer niche applications, but cannot claim to replace antibiotics line for line. We are therefore doomed to discover new antibiotics. The results of the last two decades in this field have been extremely disappointing. It is clear that the paradigm of high-throughput screening of libraries of compounds derived from industrial chemistry, while it may have worked for a number of non-infectious pathologies, has failed in the discovery of new antibiotics. What's more, even high-resolution analysis of the metabolic products of antibiotic-producing microorganisms such as Streptomyces systematically produces molecules that are already known. In addition to setting up new public-private, academic-industrial partnerships to significantly boost the research and development of new molecules, we need to open up or consolidate new avenues: the discovery and cultivation capacity of new microorganisms, particularly from soil and oceans, and the development of high-affinity inhibitors of resistance enzymes, particularly extended-spectrum beta-lactamases and carbapenemases. Time is running out..
