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

• Published in: Frontiers in cellular and infection microbiology 2022-01, Vol.11, p.789672-789672
• Main Authors: Breine, Anke, Van Gysel, Mégane, Elsocht, Mathias, Whiteway, Clémence, Philippe, Chantal, Quinet, Théo, Valcek, Adam, Wouters, Johan, Ballet, Steven, Van der Henst, Charles
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; carbapenem-resistant; Carbapenems - pharmacology; Cellular and Infection Microbiology; drug screening; Gram-negative; Harmine - pharmacology; Humans; Microbial Sensitivity Tests; pathogenic bacteria; repurposed compound
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2021.789672

The spread of antibiotic resistant bacteria is an important threat for human health. bacteria impose such a major issue, as multidrug- to pandrug-resistant strains have been isolated, rendering some infections untreatable. In this context, carbapenem-resistant bacteria were ranked as top priority by both WHO and CDC. In addition, 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 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 bacteria. A repurposing drug screen was undertaken to identify growth inhibitors. One hit was further characterized by determining the IC and testing the activity on 43 modern clinical isolates, amongst which 40 are carbapenem-resistant. 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 of 48.23 µM. In addition, HDC1 impairs growth of 43 clinical isolates. We identified a compound with inhibitory activity on all tested strains, including carbapenem-resistant clinical isolates.