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. Author manuscript; available in PMC: 2021 Mar 18.
Published in final edited form as: Acc Chem Res. 2021 Feb 26;54(6):1322–1333. doi: 10.1021/acs.accounts.0c00895

Figure 4.

Figure 4.

(A) Conversion of Ribocil C into Ribocil C-PA. WT E. coli is strain BW25113. Accumulation is reported in nmol per 1012 colony-forming units (CFUs). The s.e.m. is reported for accumulation values. (B) X-ray crystal structure of Ribocil B in complex with the FMN riboswitch aptamer of F. nucleatum suggests sites for amine installation. (C) Assessment of Ribocil C and Ribocil C-PA against a panel of multidrug-resistant clinical isolates of K. pneumoniae. MICs were performed in M9-MOPS media per CLSI guidelines. All experiments were performed in biological triplicate. (D) Sequencing of Ribocil C-PA resistant strains of E. coli reveals mutations map to the FMN riboswitch aptamer or expression platform. (E) Kaplan-Meier survival curve of mouse efficacy model of E. coli AR0493 sepsis. Statistical significance was determined by two-tailed log-rank (Mantel-Cox) test. (F) Bacterial burden model of acute pneumonia in mice infected with E. coli AR0493. Data are shown as means ± s.d. and statistical significance was determined by one-way ANOVA with Tukey’s multiple comparisons. NS, not significant (P > 0.05); ***P < 0.001; ****P < 0.0001. Reproduced with permission from ref. 3. Copyright 2020 Journal of American Chemical Society and ref. 64. Copyright 2015 Nature.