Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates

Breine, A.; Van Gysel, M.; Elsocht, M.; Whiteway, C.; Philippe, C.; Quinet, T.; Valcek, A.; Wouters, J.; Ballet, S.; Van der Henst, C.

doi:10.1101/2021.06.30.450460

bioRxiv · 10.1101/2021.06.30.450460

Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates

Breine, A.·Van Gysel, M.·Elsocht, M.·Whiteway, C.·Philippe, C.·Quinet, T.·Valcek, A.·Wouters, J.·Ballet, S.·Van der Henst, C.

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Abstract

SynopsisO_ST_ABSObjectivesC_ST_ABSThe spread of antibiotic resistant bacteria is an important threat for human healthcare. Acinetobacter baumannii bacteria impose one of the major issues, as multidrug- to pandrug-resistant strains have been found, rendering some infections untreatable. In addition, A. baumannii is a champion in surviving in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is challenging. Here, we screened a compound library to identify compounds active against recent isolates of A. baumannii bacteria. MethodsA repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining its IC50 and testing its activity on 43 recent clinical A. baumannii isolates, amongst which 40 are extensively drug- and carbapenem-resistant strains. ResultsThe repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proved to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 {micro}M. In addition, HDC1 impairs growth of all 43 recent clinical A. baumannii isolates. ConclusionsWe identified a compound with inhibitory activity on all tested, extensively drug-resistant clinical A. baumannii isolates.

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Breine, A., Van Gysel, M., Elsocht, M., Whiteway, C., Philippe, C., Quinet, T., Valcek, A., Wouters, J., Ballet, S., Van der Henst, C.. 2021-06-30. Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates. https://doi.org/10.1101/2021.06.30.450460

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