Biotransformation-guided production of quinalizarin as an antibacterial agent against Acinetobacter baumannii

Abstract

The search for antibacterial agents remains a global priority, particularly against multidrug-resistant pathogens. In this study, microbial transformation of 1,8-dihydroxyanthraquinone (chrysazin) was performed to obtain derivatives with enhanced antibacterial activity. Biotransformation using Absidia corymbifera AUMC 7104 and Beauveria bassiana AUMC 5133 yielded two metabolites: 1,2,5,8-tetrahydroxyanthraquinone (1, quinalizarin) and 1,8-dihydroxy-3-methyl-anthraquinone (2, chrysophanol), respectively. Their structures were elucidated by HRESIMS, 1D/2D NMR analyses. To the best of our knowledge, this is the first report of quinalizarin production through microbial biotransformation. The antibacterial activities of both derivatives (1 and 2), along with their parent compound, were evaluated against multidrug-resistant Acinetobacter baumannii through in vitro assays. Compound 1 exhibited the least MIC values of 512-1024 µg/mL against A. baumannii isolates and was selected for further in vivo and in silico studies. In the murine infection model, the compound 1-treated group (group IV) exhibited a significant reduction (p < 0.05) in bacterial burden compared to the positive control group (group II). Immunohistochemical analysis of kidney, liver, and spleen tissues revealed modulation of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, indicating anti-inflammatory properties alongside antibacterial activity. Molecular docking suggests a potential multi-target mechanism for compound 1, with favorable interactions with five critical bacterial proteins: MetRS, MurB, LptG/F, DXR, and MacB efflux transporter. These findings highlight quinalizarin as a potential lead compound for further antibacterial development. KEY POINTS: • Fungal biotransformation of chrysazin yielded the antibacterial agent quinalizarin. • Quinalizarin revealed in vitro and in vivo actions against Acinetobacter baumannii. • Docking studies suggested favorable interactions with multiple bacterial targets.