FIGURE SUMMARY
Title

Rifamycin O, An Alternative Anti-Mycobacterium abscessus Agent

Authors
Hanh, B.T.B., Park, J.W., Kim, T.H., Kim, J.S., Yang, C.S., Jang, K., Cui, J., Oh, D.C., Jang, J.
Source
Full text @ Molecules

Structure and 50% minimum inhibitory concentration (MIC50) values of the 23 most potent M. abscessus hits.

Structure and 50% minimum inhibitory concentration (MIC50) values of the 23 most potent M. abscessus hits.

Structure and 50% minimum inhibitory concentration (MIC50) values of the 23 most potent M. abscessus hits.

Structure and 50% minimum inhibitory concentration (MIC50) values of the 23 most potent M. abscessus hits.

Chemical structures of rifamycin analogs. Rifamycin O (A), rifabutin (B), rifampicin (C), and rifapentine (D). Red indicates hydroquinone.

In vitro activity of rifamycin O. The activity of rifamycin O (RFM O) against M. abscessus CIP 104536T R morphotype in comparison with rifabutin (RFB), rifampicin (RIF), rifapentine (RFT) and clarithromycin (CLR) in 7H9G/T/ADC. Fluorometric minimum inhibitory concentrations (MICs) were determined by fitting the RFU% sigmoidal dose–response curves. Graph fitting is representative of three independent assays, performed in triplicate.

Evaluation of in vivo RFM O activity on M. abscessus CIP 104536 R morphotype expressing mWasabi infection. Zebrafish (ZF) were infected with M. abscessus CIP 104536T R expressing mWasabi, and treated with different antibiotics. The M. abscessus infected ZF were exposed to RIF, RFT, RFM O, RFB and CLR at a concentration of 25 μM and compared to untreated controls. Green fluorescent protein (GFP) dissemination in ZF was captured using fluorescent microscopy (A). The 5 dpi embryos at 25 µM of RIF, RFT, RFM O, RFB and CLR show significant reductions in infection burden (*** P < 0.0001; ns, not significant) (B). Survival of M. abscessus-infected embryos treated at 25 μM of rifamycin analogs and clarithromycin (C) in comparison with untreated infected embryos and non-treated control (n = 20, representative of three independent experiments). * P < 0.05, *** P < 0.001.

Evaluation of in vivo RFM O activity on M. abscessus CIP 104536 R morphotype expressing mWasabi infection. Zebrafish (ZF) were infected with M. abscessus CIP 104536T R expressing mWasabi, and treated with different antibiotics. The M. abscessus infected ZF were exposed to RIF, RFT, RFM O, RFB and CLR at a concentration of 25 μM and compared to untreated controls. Green fluorescent protein (GFP) dissemination in ZF was captured using fluorescent microscopy (A). The 5 dpi embryos at 25 µM of RIF, RFT, RFM O, RFB and CLR show significant reductions in infection burden (*** P < 0.0001; ns, not significant) (B). Survival of M. abscessus-infected embryos treated at 25 μM of rifamycin analogs and clarithromycin (C) in comparison with untreated infected embryos and non-treated control (n = 20, representative of three independent experiments). * P < 0.05, *** P < 0.001.

Multiple acid-fast bacilli are present in the ZF. ZF with M. abscessus CIP 104536T R morphotype histopathological analysis was performed by Ziehl–Neelsen (acid-fast) staining. Non-treated M. abscessus CIP 104536T R-infected ZF (A). M. abscessus CIP 104536T R-infected ZF treated with RFM O (B) and CLR (C). Magnification, ×400.

Acknowledgments
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