Abstract
Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health, especially among immunocompromised populations. Given the intricate problem of dramatic increase in resistance to common biocides, the development of safe and efficient biocide formulated agents to alleviate drug resistance is highly demanding. In this study, Schiff-base ligands were successfully formed on natural biopolymer of epsilon-poly-L-lysine (e-PL) decorated aldehyde functionalized mesoporous silica SBA-15 (CHO-SBA-15) for the selective coordination of silver ions, which was affirmed by various physicochemical methods. Besides the identified broad-spectrum antibacterial activities, the as-prepared Schiff-base silver nanocomplex (CHO-SBA-15/e-PL/Ag, CLA-1) exhibited an improved inhibitory effect on infectious pathogen growth typified by Escherichia coli and Staphylococcus aureus in comparison with two control silver complexes without Schiff-base conjugates, SBA-15/e-PL/Ag and CHO-SBA-15/Ag, respectively. In addition, CLA-1 remarkably inhibited the growth of Mycobacterium tuberculosis due to the excellent antimicrobial activity of silver species. Significantly, CLA-1 kills Candida albicans cells, inhibits biofilm formation, and eliminates preformed biofilms, with no development of resistance during continuous serial passaging. The antifungal activity is connected to disruption of bacterial cell membranes and increased levels of intracellular reactive oxygen species. In mouse models of multidrug-resistant C. albicans infection, CLA-1 exhibited efficient in vivo fungicidal efficacy superior to two antifungal drugs, amphotericin B and fluconazole. Moreover, CLA-1 treatment induces negligible toxicity against normal tissues with safety. Therefore, this study reveals the pivotal role of the molecular design of Schiff-base silver nanocomplex formation on biopolymer surface-functionalized silica mesopores as a green and efficient nanoplatform to tackle infectious microbes.
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