Formation, physiology, ecology, evolution and clinical importance of bacterial persisters.
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.
KU Leuven-University of Leuven, Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, Box 2460, B-3001 Leuven, Belgium.
Bram
B
Van den Bergh
KU Leuven-University of Leuven, Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, Box 2460, B-3001 Leuven, Belgium.|Smart Systems and Emerging Technologies Unit, Department of Life Science Technologies, imec, Leuven, Belgium.
Maarten
M
Fauvart
KU Leuven-University of Leuven, Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, Box 2460, B-3001 Leuven, Belgium.
Jan
J
Michiels
D000222:Adaptation, Physiological / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D006801:Humans; D053038:Quorum Sensing / Q000502:physiology
D000900:Anti-Bacterial Agents
antibiotic crisis; antibiotic tolerance; antibiotics; bacteria; bacterial persisters