The outbreak of antibiotic-resistant bacteria, or "superbugs", poses a global public health hazard due to their resilience against the most effective last-line antibiotics. Identifying potent antibacterial agents capable of evading bacterial resistance mechanisms represents the ultimate defense strategy. This study shows that -the otherwise essential micronutrient- manganese turns into a broad-spectrum potent antibiotic when coordinated with a carboxylated nitrogen-doped graphene. This antibiotic material (termed NGA-Mn) not only inhibits the growth of a wide spectrum of multidrug-resistant bacteria but also heals wounds infected by bacteria in vivo and, most importantly, effectively evades bacterial resistance development. NGA-Mn exhibits up to 25-fold higher cytocompatibility to human cells than its minimum bacterial inhibitory concentration, demonstrating its potential as a next-generation antibacterial agent. Experimental findings suggest that NGA-Mn acts on the outer side of the bacterial cell membrane via a multimolecular collective binding, blocking vital functions in both Gram-positive and Gram-negative bacteria. The results underscore the potential of single-atom engineering toward potent antibiotics, offering simultaneously a long-sought solution for evading drug resistance development while being cytocompatible to human cells.

Department of Microbiology Faculty of Medicine and Dentistry Palacký University Olomouc Hněvotínská 3 Olomouc 779 00 Czech Republic

Department of Physical Chemistry Faculty of Science Palacký University Olomouc 17 listopadu 1192 12 Olomouc 771 46 Czech Republic

IT4Innovations VŠB Technical University of Ostrava 17 listopadu 2172 15 Ostrava Poruba 708 00 Czech Republic

Jiangsu Co Innovation Center of Efficient Processing and Utilization of Forest Resources International Innovation Center for Forest Chemicals and Materials College of Chemical Engineering Nanjing Forestry University Longpan Road 159 Nanjing 210037 P R China

Nanotechnology Centre Centre for Energy and Environmental Technologies VŠB Technical University of Ostrava 17 listopadu 2172 15 Ostrava Poruba 708 00 Czech Republic

Regional Centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacký University Olomouc Šlechtitelů 241 27 Olomouc Holice 783 71 Czech Republic

Shanghai Synchrotron Radiation Facility Shanghai Advanced Research Institute Chinese Academy of Sciences Shanghai 201204 P R China

State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou Medical College Soochow University Suzhou Jiangsu 215123 P R China

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Iron Single-Atom Catalysts Anchored on Defect-Engineered N‑Doped Graphene Reveal an Interplay between CO2 Reduction Activity and Stability