Fig. 2: Rifaximin approval is linked with the emergence of S491F.

a, Maximum-likelihood, core-SNP-based phylogeny for 4,476 VREfm inferred from 9,277 core-genome SNPs, demonstrating the presence of the S491F RpoB substitution in international VREfm. Overlaid is the region of isolation for each strain and the presence of the S491F substitution. The coloured branches indicate the three VREfm clusters identified with core genome MLST (cgMLST) used as the input for Bayesian evolutionary analyses. The scale bar indicates the number of nucleotide substitutions per site (top); an approximation of SNP distance is shown in parentheses. b, Bayesian phylodynamic analyses showing the MCC trees of the three VREfm clusters with the timing (years on x axis) of emergence for each lineage. The presence of the S491F RpoB trait for each isolate is shown in purple. Overlaid onto the MCC trees is the first instance of FDA approval for rifaximin (2004) and for hepatic encephalopathy (HE) (2010). c, Violin plots of the most recent common ancestor (MCRA) for each cluster, representing when the RpoB S491F substitution first emerged, with 95% highest-posterior density (HPD) intervals—2006 (HPD 1993–2012) for cluster 1, 2000 (HPD 1989–2008) for cluster 2, and 2004 (HPD 2001–2010) for cluster 3. Overlaid onto violin plots is the FDA approval date for rifaximin (2004).