Fig. 1: Identification of DAP-R RpoB substitutions.
From: Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin
a, Manhattan plot of 10,530 variants, displayed by their position on the reference genome and their association with DAP resistance, as determined using one-sided Fisher’s exact tests and a mixed-effects logistic regression model to correct for population structure; correction for multiple testing was performed using the Bonferroni method (dashed line). n = 998 study isolates and 2 control strains. b, The percentage of DAP-R strains with a RpoB substitution; the RRDR is shown in bold. The total number of VREfm containing each mutation is shown. c, Maximum-likelihood core-SNP-based phylogeny of clinical VREfm (n = 998 study isolates and 2 control strains) inferred from 6,574 SNPs. Overlaid are the results of in silico multi-locus sequence type (MLST), DAP phenotypic testing and RpoB substitutions associated with DAP resistance. In the first circle, ST is not shown for uncommon STs (n ≤ 5). The scale bar indicates number of nucleotide substitutions per site (top), with an approximation of SNP distance shown in parentheses. d, Rifampicin susceptibility testing results for the WT and isogenic rpoB mutants and complemented strains (designated by -C). n = 3. e, DAP susceptibility testing results for the WT and isogenic rpoB mutants and complemented strains. n = 3. The MIC for each strain is shown without error bars as there was no variation between the independent biological replicates.
