Computational and Experimental Study of Metal–Organic Frameworks (MOFs) as Antimicrobial Agents against <i>Neisseria gonorrhoeae</i>

The emergence of drug-resistant superbugs poses a critical global health threat, necessitating innovative treatment strategies. <i>Neisseria gonorrhoeae</i> (Ng) causes a sexually transmitted disease called gonorrhea, and the bacterium has shown alarming resistance to conventional antibiotics, underscoring the urgent need for novel therapeutic approaches. In the current study, we interfaced computational biology and materials science to investigate the interactions between in-house synthesized metal-organic frameworks (MOFs) and the penicillin-binding protein 2 (PBP2) of Ng, a key target for β-lactam antibiotics. Using molecular docking and interaction analyses, we identified three promising MOFs, namely, Fe-BDC-258445, Cu-BDC-687690, and Ni-BDC-638866, with optimum binding scores and stable interactions. These scores indicated strong interactions with PBP2, suggesting their potential as therapeutic agents. Antimicrobial screening using a standard disk diffusion assay demonstrated that the Cu-BDC MOFs were bactericidal for multiple strains of Ng, whereas the Ni-BDC and Fe-BDC MOFs were nonbactericidal. The Cu-BDC MOF did not kill other Gram-negative bacteria, thus demonstrating specificity for Ng, and showed low toxicity for human Chang conjunctival epithelial cells <i>in vitro</i>. No significant leaching with biological activity was observed for the Cu-BDC MOF, and microscopy demonstrated the loss of gonococcal piliation and damage to the cell membrane. These findings underscore the potential of Cu-BDC MOFs as antimicrobial agents for further development.