title: Mechanisms of bacterial persistence during stress and antibiotic exposure.
abstract: Bacterial persister cells avoid antibiotic-induced death by entering a physiologically dormant state and are considered a major cause of antibiotic treatment failure and relapsing infections. Such dormant cells form stochastically, but also in response to environmental cues, by various pathways that are usually controlled by the second messenger (p)ppGpp. For example, toxin-antitoxin modules have been shown to play a major role in persister formation in many model systems. More generally, the diversity of molecular mechanisms driving persister formation is increasingly recognized as the cause of physiological heterogeneity that underlies collective multistress and multidrug tolerance of persister subpopulations. In this Review, we summarize the current state of the field and highlight recent findings, with a focus on the molecular basis of persister formation and heterogeneity.
authors.affiliation: Center of Excellence for Bacterial Stress Response and Persistence (BASP), Department of Biology, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
authors.forename: Alexander
authors.initials: A
authors.lastname: Harms
authors.affiliation: Center of Excellence for Bacterial Stress Response and Persistence (BASP), Department of Biology, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
authors.forename: Etienne
authors.initials: E
authors.lastname: Maisonneuve
authors.affiliation: Center of Excellence for Bacterial Stress Response and Persistence (BASP), Department of Biology, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark. kgerdes@bio.ku.dk.
authors.forename: Kenn
authors.initials: K
authors.lastname: Gerdes
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018441:Biofilms; D004249:DNA Damage; D024901:Drug Resistance, Multiple, Bacterial; D006158:Guanosine Pentaphosphate / Q000378:metabolism; D018892:Proton-Motive Force; D013014:SOS Response, Genetics; D012808:Sigma Factor / Q000378:metabolism; D015398:Signal Transduction; D013269:Stochastic Processes; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D006158:Guanosine Pentaphosphate