title: Persisters: a distinct physiological state of E. coli.
abstract: BACKGROUND
  Bacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understanding persisters is encouraging, but the main obstacle in understanding their nature was our inability to isolate these elusive cells from a wild-type population since their discovery in 1944.
  
  
  RESULTS
  We hypothesized that persisters are dormant cells with a low level of translation, and used this to physically sort dim E. coli cells which do not contain sufficient amounts of unstable GFP expressed from a promoter whose activity depends on the growth rate. The dim cells were tolerant to antibiotics and exhibited a gene expression profile distinctly different from those observed for cells in exponential or stationary phases. Genes coding for toxin-antitoxin module proteins were expressed in persisters and are likely contributors to this condition.
  
  
  CONCLUSIONS
  We report a method for persister isolation and conclude that these cells represent a distinct state of bacterial physiology.
authors.affiliation: Department of Biology, Northeastern University, 134 Mugar Hall, 360 Huntington Ave, Boston, MA 02115, USA. devang@rcn.com
authors.forename: Devang
authors.initials: D
authors.lastname: Shah
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Arkady
authors.initials: A
authors.lastname: Khodursky
authors.forename: Niilo
authors.initials: N
authors.lastname: Kaldalu
authors.forename: Kristi
authors.initials: K
authors.lastname: Kurg
authors.forename: Kim
authors.initials: K
authors.lastname: Lewis
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D015169:Colony Count, Microbial; D024901:Drug Resistance, Multiple, Bacterial; D004361:Drug Tolerance; D004926:Escherichia coli / Q000166:cytology / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011401:Promoter Regions, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D049452:Green Fluorescent Proteins