Increasing concerns about the rising rates of antibiotic therapy failure and advances in single-cell analyses have inspired a surge of research into antibiotic persistence. Bacterial persister cells represent a subpopulation of cells that can survive intensive antibiotic treatment without being resistant. Several approaches have emerged to define and measure persistence, and it is now time to agree on the basic definition of persistence and its relation to the other mechanisms by which bacteria survive exposure to bactericidal antibiotic treatments, such as antibiotic resistance, heteroresistance or tolerance. In this Consensus Statement, we provide definitions of persistence phenomena, distinguish between triggered and spontaneous persistence and provide a guide to measuring persistence. Antibiotic persistence is not only an interesting example of non-genetic single-cell heterogeneity, it may also have a role in the failure of antibiotic treatments. Therefore, it is our hope that the guidelines outlined in this article will pave the way for better characterization of antibiotic persistence and for understanding its relevance to clinical outcomes.

Bacterial cells can produce and sense signal molecules, allowing the whole population to initiate a concerted action once a critical concentration (corresponding to a particular population density) of the signal has been reached, a phenomenon known as quorum sensing. One of the possible quorum sensing-regulated phenotypes is swarming, a flagella-driven movement of differentiated swarmer cells (hyperflagellated, elongated, multinucleated) by which bacteria can spread as a biofilm over a surface. The glycolipid or lipopeptide biosurfactants thereby produced function as wetting agent by reducing the surface tension. Quorum sensing systems are almost always integrated into other regulatory circuits. This effectively expands the range of environmental signals that influence target gene expression beyond population density. In this review, we first discuss the regulation of AHL-mediated surface migration and the involvement of other low-molecular-mass signal molecules (such as the furanosyl borate diester AI-2) in biosurfactant production of different bacteria. In addition, population density-dependent regulation of swarmer cell differentiation is reviewed. Also, several examples of interspecies signalling are reported. Different signal molecules either produced by bacteria (such as other AHLs and diketopiperazines) or excreted by plants (such as furanones, plant signal mimics) might influence the quorum sensing-regulated swarming behaviour in bacteria different from the producer. On the other hand, specific bacteria can reduce the local available concentration of signal molecules produced by others. In the last part, the role and regulation of a surface-associated movement in biofilm formation is discussed. Here we also describe how quorum sensing may disperse existing biofilms and control the interaction between bacteria and higher organisms (such as the Rhizobium-bean symbiosis).

Persisters are transiently antibiotic-tolerant cells that complicate the treatment of bacterial infections. Both theory and experiments have suggested that persisters facilitate genetic resistance by constituting an evolutionary reservoir of viable cells. Here, we provide evidence for a strong positive correlation between persistence and the likelihood to become genetically resistant in natural and lab strains of E. coli. This correlation can be partly attributed to the increased availability of viable cells associated with persistence. However, our data additionally show that persistence is pleiotropically linked with mutation rates. Our theoretical model further demonstrates that increased survival and mutation rates jointly affect the likelihood of evolving clinical resistance. Overall, these results suggest that the battle against antibiotic resistance will benefit from incorporating anti-persister therapies.

Certain infectious diseases caused by pathogenic bacteria are typically chronic in nature. Potentially deadly examples include tuberculosis, caused by Mycobacterium tuberculosis, cystic fibrosis-associated lung infections, primarily caused by Pseudomonas aeruginosa, and candidiasis, caused by the fungal pathogen Candida albicans. A hallmark of this type of illness is the recalcitrance to treatment with antibiotics, even in the face of laboratory tests showing the causative agents to be sensitive to drugs. Recent studies have attributed this treatment failure to the presence of a small, transiently multidrug-tolerant subpopulation of cells, so-called persister cells. Here, we review our current understanding of the role that persisters play in the treatment and outcome of chronic infections. In a second part, we offer a perspective on the development of anti-persister therapies based on genes and mechanisms that have been implicated in persistence over the last decade.

Persisters are transiently tolerant variants that allow populations to avoid eradication by antibiotic treatment. Their antibiotic tolerance is non-genetic, not inheritable and results from a phenotypic switch from the normal, sensitive cell type to the tolerant, persister state. Here we give a comprehensive overview on bacterial persistence. We first define persistence, summarize the various aspects of persister physiology and show their heterogeneous nature. We then focus on the role of key cellular processes and mechanisms controlling the formation of a subpopulation of tolerant cells. Being a prime example of a risk-spreading strategy, we next discuss the eco-evolutionary aspects of persistence, e.g. how persistence evolves in the face of treatment with antibiotics. Finally, we illustrate the clinical importance of persisters, as persistence is worsening the worldwide antibiotic crisis by prolonging antibiotic treatment, causing therapy failure or catalyzing the development of genetically encoded antibiotic resistance. A better understanding of this phenotype is critical in our fight against pathogenic bacteria and to obtain a better outlook on future therapies.