Big Questions in Microbiology

The spread of drug-resistant microbes and spectre of a ‘‘post-antibiotic’’ world have made the fight against antimicrobial resistance (AMR) one of the most important scientific challenges of our time. The threat of AMR has raised critical questions that are profoundly influencing the research agenda in all spheres of microbiology. For instance, the development of new intervention strategies against AMR demands a deeper understanding of host-pathogen relationships and how they evolve during the course of transmission, infection, and disease, as well as insight into the interplay between and among pathogens and other microbes within their host and environmental ecosystems. Likewise, paving theway toward sterilizing therapies that are effective and fast-acting requires that we come to grips with the microbial factors that mitigate antibiotic efficacy, which include, but are not restricted to, persistence and drug metabolism, permeation, and efflux. In the case of bacterial persistence, we need to move from an essentially operational definition of this phenomenon toward mechanistic understanding of the genesis, physiology, and metabolic state of persister cells that can survive prolonged exposure to bactericidal antibiotics and of the role, if any, that drugs might play in this phenomenon. At this time of spectacular technological advancement and revolutionary change in our view of themicrobial world, I believe that microbiologists are poised to tackle these questions head on.