AUTHOR=Wang Jie , Gong Rui , Yang Ming , Wu Xi , Li Ziwei , Huang Haibing , Yan Xiyun , Wang Daji 

TITLE=A ruthenium single atom nanozyme-based antibiotic for the treatment of otitis media caused by Staphylococcus aureus

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1439039

DOI=10.3389/fchem.2024.1439039

ISSN=2296-2646

ABSTRACT=<p><italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C<sub>3</sub>N<sub>4</sub> SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C<sub>3</sub>N<sub>4</sub>. These metal-C<sub>3</sub>N<sub>4</sub> display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C<sub>3</sub>N<sub>4</sub> demonstrates the optimal peroxidase-like activity (285.3 U mg<sup>–1</sup>), comparable to that of horseradish peroxidase (267.7 U mg<sup>–1</sup>). <italic>In vitro</italic> antibacterial assays reveal that Ru-C<sub>3</sub>N<sub>4</sub> significantly inhibits <italic>S. aureus</italic> growth compared with other metal-C<sub>3</sub>N<sub>4</sub> even at a low concentration (0.06 mg mL<sup>–1</sup>). Notably, Ru-C<sub>3</sub>N<sub>4</sub> acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by <italic>S. aureus</italic> are easily degraded by Ru-C<sub>3</sub>N<sub>4</sub> due to its high peroxidase-like activity. <italic>In vivo</italic>, Ru-C<sub>3</sub>N<sub>4</sub> effectively eliminates <italic>S. aureus</italic> and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C<sub>3</sub>N<sub>4</sub> does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate <italic>S. aureus</italic> and treat <italic>S. aureus</italic>-induced OM.</p>