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

Abstract

ObjectivesThe 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.MethodsA 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.ResultsThe 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.ConclusionsWe identified a compound with inhibitory activity on all tested strains, including carbapenem-resistant clinical A. baumannii isolates.

Bactericidal effect of bacteria isolated from the marine sponges Hymeniacidon perlevis and Halichondria panicea against carbapenem-resistant Acinetobacter baumannii

“…The 114 bacterial strains used in this study, detailed in Supplementary Table S1, were previously isolated and characterized (Rodriguez Jimenez et al, 2021, 2022. Seven A. baumannii strains were used: two reference strains (the standard model strain ATCC19606-VUB (Hamidian et al, 2020), the carbapenem-resistant, virulent and capsulated AB5075 derivative AB5075-VUB (Jacobs et al, 2014;Gallagher et al, 2015)) and five carbapenem-resistant clinical isolates (AB176-VUB, AB177-VUB, AB183-VUB, AB212-VUB and AB224-VUB (Valcek et al, 2022)).…”

“…and Vagococcus (5 isolates; 12B2, 25B2, 35B2, 36B2, and 110B2). To test the broad activity against recent and clinically relevant CRAb isolates, antibacterial activity of the inhibitory strains was further assayed against 5 recent clinical A. baumannii strains (AB176-VUB, AB177-VUB, AB183-VUB, AB212-VUB, AB224-VUB) and one other broadly used strain ATCC19606-VUB (Breine, 2022;Valcek et al, 2022). All sponge-derived bacterial isolates that impair the growth of AB5075-VUB also inhibit the five other CRAb bacterial isolates and the reference strain ATCC19606-VUB, showing its broad activity.…”