AUTHOR=Breine Anke , Van Gysel Mégane , Elsocht Mathias , Whiteway Clémence , Philippe Chantal , Quinet Théo , Valcek Adam , Wouters Johan , Ballet Steven , Van der Henst Charles 

TITLE=Antimicrobial Activity of a Repurposed Harmine-Derived Compound on Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.789672

DOI=10.3389/fcimb.2021.789672

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>The spread of antibiotic resistant bacteria is an important threat for human health. <italic>Acinetobacter baumannii</italic> bacteria impose such a major issue, as multidrug- to pandrug-resistant strains have been isolated, rendering some infections untreatable. In this context, carbapenem-resistant <italic>A. baumannii</italic> bacteria were ranked as top priority by both WHO and CDC. In addition, <italic>A. baumannii</italic> bacteria survive 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 <italic>A. baumannii</italic> isolates, the search for new antibacterials is very challenging because of the requirement of drug target conservation amongst the different strains. Here, we screened a chemical library to identify compounds active against several reference strains and carbapenem-resistant <italic>A. baumannii</italic> bacteria.</p></sec><sec><title>Methods</title><p>A repurposing drug screen was undertaken to identify <italic>A. baumannii</italic> growth inhibitors. One hit was further characterized by determining the IC<sub>50</sub> and testing the activity on 43 modern clinical <italic>A. baumannii</italic> isolates, amongst which 40 are carbapenem-resistant.</p></sec><sec><title>Results</title><p>The repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proves to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC<sub>50</sub> of 48.23 µM. In addition, HDC1 impairs growth of 43 clinical <italic>A. baumannii</italic> isolates.</p></sec><sec><title>Conclusions</title><p>We identified a compound with inhibitory activity on all tested strains, including carbapenem-resistant clinical <italic>A. baumannii</italic> isolates.</p></sec>