Persistent bacterial infections and persister cells

• Published in: Nature reviews. Microbiology Vol. 15; no. 8; pp. 453 - 464
• Main Authors: Fisher, Robert A., Gollan, Bridget, Helaine, Sophie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2017; Nature Publishing Group
• Subjects: 631/326/107; 631/326/22/1290; 631/326/41/1969; 631/326/41/1969/2038; 631/326/41/2529; 631/326/41/88; 692/699/255; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; Bacteria; Bacteria - drug effects; Bacteria - growth & development; Bacteria - metabolism; Bacteria - pathogenicity; Bacterial diseases; Bacterial infections; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Care and treatment; Development and progression; Drug Resistance, Multiple, Bacterial; Environmental changes; Heterogeneity; Host-bacteria relationships; Humans; Immune response; Immunosuppression; Infections; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Observations; Parasitology; Pathogens; Persistent infection; Regrowth; review-article; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro.2017.42

Key Points
Many bacterial infections persist in the host for long periods of time despite antibiotic treatment.
This persistence is an important medical concern, as it leads to the overuse of antibiotics and therefore contributes to antimicrobial resistance.
The role of antibiotic-tolerant persister cells in the recalcitrance and relapse of bacterial infections has gained recognition in recent years.
Persisters are often growth-arrested bacteria with a reduced metabolism that are able to restart growth after a stress.
The stresses that bacteria encounter during the infection of a host are triggers for the formation of persisters.
Toxin–antitoxin modules have an important role in the formation of growth-arrested persisters.
Understanding how growth-arrested persisters regrow is necessary to design better therapeutic strategies.
Many bacteria can infect and persist inside their hosts for long periods of time. In this Review, Fisher, Gollan and Helaine discuss recent developments in our understanding of bacterial persisters and their potential implications for the treatment of persistent infections.
Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. The formation of persister cells establishes phenotypic heterogeneity within a bacterial population and has been hypothesized to be important for increasing the chances of successfully adapting to environmental change. The presence of persister cells can result in the recalcitrance and relapse of persistent bacterial infections, and it has been linked to an increase in the risk of the emergence of antibiotic resistance during treatment. If the mechanisms of the formation and regrowth of these antibiotic-tolerant cells were better understood, it could lead to the development of new approaches for the eradication of persistent bacterial infections. In this Review, we discuss recent developments in our understanding of bacterial persisters and their potential implications for the treatment of persistent infections.