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Fig 1.

Screening validation.

The Z-factor of 0.7 demonstrates excellent assay.

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Fig 2.

Screening of the Pathogen Box library for Mycobacterium abscessus.

Scatter plot distribution showing the results of the M. abscessus screening of the Pathogen Box library using resazurin reduction assay. A total of 400 compounds from the Pathogen Box were screened at 20 μM against M. abscessus. Growth inhibition of at least 80% was defined as cut-off which resulted in 4 hits (1.0% hit rate) from the 400 compounds in the Pathogen Box library.

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Fig 2 Expand

Fig 3.

Dose response curve (DRC) and chemical structure of hits.

Dose response curve of MMV687146 (A), MMV688508 (B), MMV688844 (C), and MMV688845 (D) and reference compound (Amikacin; E) were plotted and chemical structure of each compounds were described.

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Fig 4.

In vitro activity of MMV688844.

Activity of MMV688844 against Mycobacterium abscessus clinical isolates. Dose-response curves were plotted from REMA data for M. abscessus strains treated with MMV688844. Data are expressed as the mean ± standard deviation (SD) of triplicates for each concentration. RFU, relative fluorescence units.

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Fig 5.

Time–kill curves of (A) cefoxitin and (B) MMV688844 against Mycobacterium abscessus. The bacteria were grown in liquid culture (Middlebrook 7H9 medium) in the presence of the indicated concentrations of cefoxitin or MMV688844.

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Fig 5 Expand