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ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 2008, p. 27182726 Vol. 52, No. 8 0066-4804/08/$08.00 0 doi:10.1128/AAC.00144-08

Summary: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 2008, p. 2718­2726 Vol. 52, No. 8
0066-4804/08/$08.00 0 doi:10.1128/AAC.00144-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Role of Global Regulators and Nucleotide Metabolism in Antibiotic
Tolerance in Escherichia coli
Sonja Hansen, Kim Lewis, and Marin Vulic´*
Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts 02115
Received 1 February 2008/Returned for modification 26 February 2008/Accepted 25 May 2008
Bacterial populations produce a small number of persister cells that exhibit multidrug tolerance. Persister
cells are largely responsible for the antibiotic recalcitrance of biofilm infections. The mechanism of persister
cell formation largely remains unknown due to the challenges in identifying persister genes. We screened an
ordered comprehensive library of 3,985 Escherichia coli knockout strains to identify mutants with altered
antibiotic tolerance. Stationary-state cultures in 96-well plates were exposed to ofloxacin at a concentration
which allows only tolerant persister cells to survive. The persister cell level of each culture was determined. A
total of 150 mutants with decreased persistence were identified in the initial screen, and subsequent validation
confirmed that neither the growth rate nor the ofloxacin MIC was affected for 10 of them. The genes affected
in these strains were dnaJ and dnaK (chaperones), apaH (diadenosine tetraphosphatase), surA (peptidyl-prolyl
cis-trans isomerase), fis and hns (global regulators), hnr (response regulator of RpoS), dksA (transcriptional
regulator of rRNA transcription), ygfA (5-formyl-tetrahydrofolate cyclo-ligase), and yigB (flavin mononucle-
otide [FMN] phosphatase). The prominent presence of global regulators among these strains pointed to the


Source: Ayers, Joseph - Marine Science Center & Department of Biology, Northeastern University


Collections: Engineering