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

Objectives: The spread of antibiotic resistant bacteria is an important threat for human health. Acinetobacter baumannii bacteria impose such a major issue, as multidrug- to pandrug-resistant strains have been isolated, rendering some infections untreatable. In this context, carbapenem-resistant A. baumannii bacteria were ranked as top priority by both WHO and CDC. In addition, A. baumannii 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 A. baumannii 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 A. baumannii bacteria. Methods: A repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining the IC₅₀ and testing the activity on 43 modern clinical A. baumannii isolates, amongst which 40 are carbapenem-resistant. Results: 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 IC₅₀ of 48.23 µM. In addition, HDC1 impairs growth of 43 clinical A. baumannii isolates. Conclusions: We identified a compound with inhibitory activity on all tested strains, including carbapenem-resistant clinical A. baumannii isolates.