A problem of persistence: still more questions than answers?

Bacterial persistence poses a major obstacle for current efforts to tackle the global rise of antibiotic resistance. Here, Balaban, Gerdes, Lewis and McKinney discuss the physiological features of persister cells and the factors leading to their emergence, as well as the implications of persistence for antibiotic treatment regimens and bacterial heterogeneity. The current antibiotic resistance crisis has led to increased pressure to prioritize strategies to tackle the issue, with a strong focus being placed on the development of novel antimicrobials. However, one major obstacle that is often overlooked is persister cells, which are refractory to antibiotic treatment. Tackling persistence is a challenge because these cell types are extremely difficult to study and, consequently, little is known about their physiology and the factors that lead to their emergence. Here, four experts contemplate the main physiological features that define persistence and the implications of persistence for antibiotic treatment regimens, and consider what the study of bacterial persistence has taught us about the heterogeneity of bacterial populations.