Spinel-Structured MnCo₂O₄ 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, MnCo₂O₄ 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 MnCo₂O₄ 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 MnCo₂O₄ 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, MnCo₂O₄ NCs represent a promising therapeutic nanomaterial for bacterial infection management.