Spinel‐Structured MnCo ₂ O ₄ Nanoclusters Mediate Multimodal and Efficient Suppression of Drug‐Resistant Bacteria

ABSTRACT The global dissemination of bacterial antibiotic resistance has emerged as a formidable public health challenge. According to the World Health Organization (WHO), drug‐resistant infections claim over 1.3 million lives annually, with projections indicating this number could rise to 10 million by 2050. Multi‐drug resistant (MDR) bacteria accelerate resistance propagation through a biofilm formation process implicated in over 80% of microbial infections coupled with efflux pump activation and genetic mutations. The biofilm's physical barrier reduces antibiotic penetration efficiency by over 90%, while sluggish therapeutic development and clinical antibiotic misuse synergistically exacerbate antimicrobial resistance. In this study, MnCo ₂ O ₄ nanoclusters (NCs) with uniform particle size, excellent dispersibility, and structural stability were synthesized via a high‐temperature thermal decomposition. These NCs demonstrated exceptional biocompatibility and potent antibacterial activity. Mechanistic investigations revealed that MnCo ₂ O ₄ NCs effectively eradicate biofilms, enhance reactive oxygen species (ROS) generation, disrupt bacterial cell membranes, and induce nucleic acid leakage, ultimately leading to bacterial death. Further molecular studies elucidated that MnCo ₂ O ₄ NCs interfere with bacterial energy metabolism, cell wall synthesis, and nitrogen utilization pathways while inducing ribosomal protein translation arrest, thereby effectively suppressing the development of bacterial resistance. Collectively, MnCo ₂ O ₄ NCs represent a promising therapeutic nanomaterial for bacterial infection management.