Abstract Background Acinetobacter baumannii is the primary cause of persistent opportunistic infections in healthcare settings, recognized as a global priority due to its resistance to antibiotic therapy. Quorum sensing and biofilm formation are the key factors driving the pathogenesis and drug resistance of A. baumannii . Nanostructures demonstrated encouraging promise in enhancing the therapeutic efficacy and overcoming treatment failure. Therefore, the efficacy of staphyloxanthin (STX)-encapsulated niosomes was evaluated both in vitro and in vivo. Results The formulated niosomal nanovesicles displayed a spherical shape at the nanoscale (177.8 nm), featuring a slow-release rate (39.6%) and appropriate entrapment efficiency (92.7%). Our results demonstrated that STX exhibited strong antibacterial activity, with MIC values up to 16 µg/mL against multidrug-resistant isolates ( n = 24). The in vitro findings revealed that the encapsulation of STX within niosomal nanovesicles demonstrated superior therapeutic efficacy compared to the free solution. This improvement was reflected by a significant reduction in biofilm formation (68–88%), motility (66.66–94.45%), and siderophore production (48.75–79.5%), as well as marked disruption of the mature biofilm by 82%. The anti-quorum sensing activity of STX was further confirmed the attenuation of biofilm and virulence, as evidenced by downregulation of abaI expression (1.42-fold reduction) and molecular docking simulations. It is noteworthy that the biological findings revealed a significant eradication of meropenem-induced persister cells after the addition of niosomal dispersion. The preclinical investigations prove the efficacy of STX in improving survival rates through reducing the bacterial burden (2-fold reduction) and lethal inflammatory consequences in a mouse model of pneumonia. Conclusion our results suggested that STX may serve as a promising alternative for combating A. baumannii biofilms and persister cells.
Nosair et al. (2025) studied this question.