Open Access Research article

The association of DNA damage response and nucleotide level modulation with the antibacterial mechanism of the anti-folate drug Trimethoprim

Dipen P Sangurdekar1, Zhigang Zhang34 and Arkady B Khodursky23*

Author Affiliations

1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, 132 Carl C. Icahn Laboratory, Princeton University, Washington Road, Princeton NJ 08540, USA

2 Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Ave, Saint Paul, MN 55108, USA

3 Biotechnology Institute, University of Minnesota, 1479 Gortner Ave, Saint Paul, MN 55108, USA

4 Metabolix Inc., 21 Erie Street, Cambridge, MA 02139, USA

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BMC Genomics 2011, 12:583  doi:10.1186/1471-2164-12-583

Published: 28 November 2011

Additional files

Additional file 1:

Gene Sets. A list of gene sets used in the analysis and individual genes that make up sets. The file contains two excel sheets: "Gene Sets" enumerates all classified sets; "Gene Set membership" classifies genes into sets: 1 - a member, 0 - not a member.

Format: XLS Size: 12.7MB Download file

This file can be viewed with: Microsoft Excel Viewer

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Additional file 2:

Analysis code. R code used for the analysis of the data and tools for retrieving individual gene set scores and generating plots.

Format: ZIP Size: 4.2MB Download file

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Additional file 3:

Coefficients of a set score linear model on individual supplements. Set scores and set coefficients obtained from the linear model employed to assess the effects of individual supplements (as described in main text).

Format: XLS Size: 36KB Download file

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Additional file 4:

Gene Sets associated with the lethality phenotype. List of gene sets up-regulated in bacteriostatic or bactericidal conditions along with their linear model coefficients.

Format: XLS Size: 19KB Download file

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Additional file 5:

Plots of gene set scores associated with the lethality phenotype. Boxplots identifying the set score differences between static and cidal conditions.

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Additional file 6:

Comparison of non-parametric (AUC) and parametric (linear model FDR) significant tests for sets. Scatter plot of AUC scores and False Discovery Rates (FDR) from the linear model indicating strong correlation between the two measures of association between set scores and cell phenotype.

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Additional file 7:

O.D. values of deo mutants after TMP treatment in M9 and LB media. A) LBTMP treatment. Increase in O.D. (600 nm) after 50 μg/ml TMP treatment of wild-type MG1655 strain (blue), deoA (red), deoC (green) and deoR (purple) knock-out mutants in LB medium. TMP was added to respective cultures grown from overnight inoculum to mid-log phase in LB medium at O.D. 0.37-0.42 (Time 0 hr). B) M9TMPAdAA treatment. Increase in O.D. (600 nm) after 25 μg/ml TMP treatment of wild-type MG1655 strain (blue), deoA (red), deoC (green) and deoR (purple) knock-out mutants in M9 medium. TMP was added to respective cultures grown from overnight inoculum to mid-log phase in M9 medium at O.D. 0.25-0.35 (Time 0 hr).

Format: PDF Size: 159KB Download file

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