Supplementary Materials

Clinically relevant mutations in core metabolic genes confer antibiotic resistance

Allison J. Lopatkin, Sarah C. Bening, Abigail L. Manson, Jonathan M. Stokes, Michael A. Kohanski, Ahmed H. Badran, Ashlee M. Earl, Nicole J. Cheney, Jason H. Yang, James J. Collins

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • Materials and Methods
  • Figs. S1 to S11
  • Tables S1 and S2
  • Captions for Tables S3 to S15
  • References
Data Table S3
Sequencing maps for classic and metabolic evolutions. Sheet one has sequencing maps for the main classic and metabolic evolutions. Sheet two has the sequencing map for the static metabolic evolution.
Data Table S4
Sequencing results for classic evolution. Sheet one has master data. Sheet two has WT genotype for two replicates. In all subsequent results, tabulations exclude mutations that appeared in the WT strain (dicC and rbsR).
Data Table S5
Classic evolution sequencing with KEGG classifications. KEGG and BRITE hierarchy classifications included for the classic evolution sequencing results. Sheet one lists all genes by sample group, and sheet two lists all KEGG functional groups with each associated gene.
Data Table S6
Sequencing results for metabolic evolution. Column 'evol_exp' designates rich (2_2M) or minimal media (2_1M).
Data Table S7
Sequencing results for metabolic evolution with static temperature. Sheet one contains master data. Sheet two contains the unique genes for each treatment group.
Data Table S8
Gene ontology (GO) enrichment for biological processes results. Gene list for GO enrichment from classical evolution. First sheet has data used in Fig. 3B-C. Gray shading indicates rows used for plotting. Sheet two has the list of genes from the metabolic evolution used for GO enrichment and sheet three has the list of genes from the classic evolution used for GO enrichment.
Data Table S9
Comprehensive list of all NCBI pathogens used in the comparative analysis.
Data Table S10
Comparative analysis for top genes with >= 1 hit in NCBI pathogen list. Table includes gene name, mutation, number in clinical isolates, number in total isolates, P-value, and corrected P-value. Yellow rows highlight those used for subsequent validation experiments.
Data Table S11
Metabolic and canonical gene co-occurrence likelihood. Number of strains that had a mutation in canonical-canonical, metabolic-metabolic, or one of each, was tabulated. Fisher's exact test was used to calculate likelihood of co-occurring mutations.
Data Table S12
Raw gene count output from FeatureCounts for each of the 12 samples.
Data Table S13
Differential gene expression for pair-wise sample comparison. Log-2 transformed and TMM-normalized CPM for WT and sucAM cells with and without treatment. Differential expression was determined between treated and untreated conditions for each strain-type.
Data Table S14
GO enrichment for treated WT compared to sucAM. Sheet one contains the corresponding list of genes in the order they were clustered (Fig. 4C). Sheet two contains GO pathway enrichment for all differentially expressed genes between carb-treated WT and sucAM.
Data Table S15
Gene tabulation across conditions. Sheet contains representative metabolic and canonical mutations along with the conditions in which they occurred; closely related genes are included (e.g., sucA and satP). Sheet two contains the number of unique genes identified from each condition, along with the overlap between conditions. UN is untreated control.
MDAR Reproducibility Checklist