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. 2023 Aug 10;21(8):e3002186. doi: 10.1371/journal.pbio.3002186

Fig 1. Albicidin high-level resistance resulting from GDAs in evolved S. Typhimurium.

Fig 1

(A) Comparison of albicidin MICs for WT and evolved S. Typhimurium strains (see Fig C and Table B in S1 Text). A structure of albicidin and azahistidine albicidin is included in the bar diagram. (B) Nanopore sequencing revealed 7 copies of the GDA region in the evolved tsx-deficient S. Typhimurium strain T12 (see below, T12), including the genes between topoisomerase IV subunits A and B (see above, WT). The common approximately 2,200 bp long region present in all 6 evolved strains (S41, T01, T04, T05, T10, and T12) is highlighted in cyan. It includes 3 genes: STM3175, ygiW, and partly qseB. (C) Arabinose-induced overexpression of STM3175 (cyan), but not YgiW (light green) or QseBC (olive), results in an elevated albicidin MIC in S. Typhimurium WT. (D) Arabinose-induced overexpression of the LBD (cyan), but not of the DBD (blue) of STM3175 revealed and increased MIC against albicidin in S. Typhimurium. (E) Crystal structure of STM3175 with the conserved AraC-type DBD and GyrI-like LBD shown in gray and cyan, respectively (please also see Fig M in S1 Text). Source data are provided as a source data file (S1 Data). DBD, DNA-binding domain; GDA, gene duplication–amplification; MIC, minimum inhibitory concentration; LBD, ligand-binding domain; WT, wild-type.