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The TCA cycle is not required for selection or survival of multidrug-resistant Salmonella
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Ricci, V., Loman, Nicholas J., Pallen, Mark J., Ivens, Alasdair, Fookes, M., Langridge, G. C., Wain, J. and Piddock, Laura J. V. (2011) The TCA cycle is not required for selection or survival of multidrug-resistant Salmonella. Journal of Antimicrobial Chemotherapy, Volume 67 (Number 3). pp. 589-599. doi:10.1093/jac/dkr515 ISSN 0305-7453.
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Official URL: http://dx.doi.org/10.1093/jac/dkr515
Abstract
Objectives:
The initial aim of this study was to use a systems biology approach to analyse a ciprofloxacin-selected multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium, L664.
Methods:
The whole genome sequence and transcriptome of L664 were analysed. Site-directed mutagenesis to recreate each mutation was carried out, followed by phenotypic characterization and mutation frequency analysis. As a mutation in the TCA cycle was detected we tested the controversial hypothesis regarding the bacterial response to bactericidal antibiotics, put forward by Kohanski et al. (Cell 2007; 130: 797–810 and Mol Cell 2010; 37: 311–20), that exposure of bacteria to agents such as ciprofloxacin produces reactive oxygen species (ROS), which transiently increase the mutation rate giving rise to MDR bacteria.
Results:
L664 contained a mutation in ramR that conferred MDR. A mutation in tctA affected the TCA cycle and conferred the inability to grow on minimal agar. The virulence of L664 was not attenuated. Ciprofloxacin exposure produced ROS in L664 and SL1344 (tctA::aph), but it was reduced and occurred later. There were no significant differences in the rates of killing or mutations per generation to antibiotic resistance between the strains.
Conclusions:
Whilst we confirm production of ROS in response to ciprofloxacin, we have no data to support the hypothesis that this leads to selection of MDR strains. Our results indicate that the mutations in tctA and glgA were random as they did not pre-exist in the parental strain, and that the mutation in tctA did not provide a survival advantage or disadvantage in the presence of antibiotic.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QR Microbiology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Drug resistance in microorganisms , Salmonella -- Genetics | ||||
Journal or Publication Title: | Journal of Antimicrobial Chemotherapy | ||||
Publisher: | Oxford University Press | ||||
ISSN: | 0305-7453 | ||||
Official Date: | 2011 | ||||
Dates: |
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Volume: | Volume 67 | ||||
Number: | Number 3 | ||||
Page Range: | pp. 589-599 | ||||
DOI: | 10.1093/jac/dkr515 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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