Persisters: a distinct physiological state of E. coli.
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.
Shah
Devang
D
Department of Biology, Northeastern University, 134 Mugar Hall, 360 Huntington Ave, Boston, MA 02115, USA. devang@rcn.com
Zhang
Zhigang
Z
Khodursky
Arkady
A
Kaldalu
Niilo
N
Kurg
Kristi
K
Lewis
Kim
K
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
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D049452:Green Fluorescent Proteins