Triple-synergy bactericidal action: a mannose-decorated bioinspired coating on silver-mesoporous silica for eradicating multidrug-resistant Mycobacterium tuberculosis

Abstract

Tuberculosis, the world's leading cause of death from a single infectious agent in 2023, is exacerbated by the rising prevalence of multidrug-resistant (MDR) Mycobacterium tuberculosis, underscoring an urgent need for novel therapeutic agents. In this study, we developed a green in situ synthesis strategy for silver nanoparticles (Ag NPs) utilizing polydopamine (PDA) as a biomimetic reducing and coating agent on mesoporous silica (SBA-15). The material was further co-coated with the antimicrobial polymer epsilon-poly-L-lysine (EPL) and functionalized with mannose via a Schiff-base reaction. The resulting composite, denoted as Ag@SBA-15/Man-PDA-EPL, was comprehensively characterized by physicochemical techniques and exhibited low cytotoxicity. Mycobacterium tuberculosis (H37Rv and MDR) was used for the evaluation of the prepared nanocomposites in which the components (Ag@SBA-15/PDA and EPL) exhibited synergistic effect towards MDR. The mannose-grafted composite (Ag@SBA-15/Man-PDA-EPL) exhibited significantly enhanced anti-tubercular efficacy compared to its non-functionalized counterpart (Ag@SBA-15/PDA-EPL), an improvement attributed to the antibacterial capability conferred by the Schiff-base formation. Transmission electron microscopy (TEM) imaging confirmed extensive cellular damage in mycobacteria treated with Ag@SBA-15/Man-PDA-EPL. This study validates a rational combination strategy integrating silver nanoparticles, EPL, and ligand-specific targeting via a Schiff-base moiety into a unified nanoplatform, offering a promising approach to combat drug-resistant tuberculosis and mitigate nosocomial infections.