More than 70 years ago, Hobby 1 and Bigger 2 observed that antibiotics that are considered bactericidal and kill bacteria in fact fail to sterilize cultures. Bigger realized that the small number of bacteria that manage to survive intensive antibiotic treatments are a distinct subpopulation of bacteria that he named 'persisters'. Fuelled in part by increasing concerns about antibiotic resistance but also by technological advances in single-cell analyses, the past 15 years have witnessed a great deal of research on antibiotic persistence by investigators with different backgrounds and perspectives. As the number of scientists that tackle the puzzles and challenges of antibiotic persistence from many different angles has profoundly increased, it is now time to agree on the basic definition of persistence and its distinction from the other mechanisms by which bacteria survive exposure to bactericidal antibiotic treatments 3. Several approaches have independently emerged to define and measure persistence. Research groups following seemingly similar procedures may reach different results, and careful examination of the experimental procedures often reveals that results of different groups cannot be compared. During the European Molecular Biology Organization (EMBO) Workshop 'Bacterial Persistence and Antimicrobial Therapy' (10-14 June 2018) in Ascona, Switzerland, which brought together 121 investigators involved in antibiotic persistence research from 21 countries, a discussion panel laid the main themes for a Consensus Statement on the definition and detection procedure of antibiotic persistence detailed below. In light of the potential role that antibiotic persistence can have in antibiotic treatment regimens, it is our hope that clarification and standardization of experimental procedures will facilitate the translation of basic science research into practical guidelines. Defining the persistence phenomena We adopt here a phenomenological definition of antibiotic persistence that is based on a small set of observations that can be made from experiments performed in vitro and that does not assume a specific mechanism. We focus on the differences and similarities between antibiotic persistence and other processes enabling bacteria to survive exposure to antibiotic treatments that could kill them, such as resistance, tolerance and heteroresistance. We identify different types of persistence that should be measured differently to obtain meaningful results; therefore, the definition of these types goes beyond semantics. For the more mathematically oriented readers, we provide a mathematical definition of the

Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody-antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody-antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections.

By exploiting the ability of Pseudomonas aeruginosa to infect a variety of vertebrate and nonvertebrate hosts, we have developed model systems that use plants and nematodes as adjuncts to mammalian models to help elucidate the molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable degree of conservation in the virulence mechanisms used by P. aeruginosa to infect hosts of divergent evolutionary origins.

Barley Rar1 is a convergence point in the signaling of resistance to powdery mildew, triggered by multiple race-specific resistance (R) genes. Rar1 is shown to function upstream of H2O2 accumulation in attacked host cells, which precedes localized host cell death. We isolated Rar1 by map-based cloning. The sequence of the deduced 25.5 kDa protein reveals two copies of a 60-amino acid domain, CHORD, conserved in tandem organization in protozoa, plants, and metazoa. CHORD defines a novel eukaryotic Zn2+-binding domain. Silencing of the C. elegans CHORD-containing gene, chp, results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development. Our findings indicate that plant R genes have recruited a fundamental cellular control element for signaling of disease resistance and cell death.