Single Atom Engineered Antibiotics Overcome Bacterial Resistance.

Area of Science:

• Materials Science
• Nanotechnology
• Microbiology
• Drug Discovery

Background:

• Antibiotic-resistant bacteria (superbugs) present a critical global health threat.
• Existing last-line antibiotics are becoming ineffective against these resilient pathogens.
• Developing novel antibacterial agents that circumvent resistance mechanisms is essential.

Purpose of the Study:

• To investigate manganese coordinated with carboxylated nitrogen-doped graphene (NGA-Mn) as a potent broad-spectrum antibiotic.
• To evaluate NGA-Mn's efficacy against multidrug-resistant bacteria and its potential to evade resistance development.
• To assess the cytocompatibility of NGA-Mn with human cells.

Main Methods:

• Synthesis of NGA-Mn by coordinating manganese with carboxylated nitrogen-doped graphene.
• Testing NGA-Mn's antibacterial activity against a wide spectrum of multidrug-resistant bacteria.
• In vivo wound infection healing assays.
• Cytotoxicity assays on human cells.
• Mechanistic studies on bacterial cell membrane interaction.

Main Results:

• NGA-Mn demonstrated broad-spectrum inhibition of multidrug-resistant bacterial growth.
• The material effectively healed bacterial-infected wounds in vivo.
• NGA-Mn exhibited significantly higher cytocompatibility (up to 25-fold) with human cells compared to its minimum inhibitory concentration.
• The antibiotic material evaded bacterial resistance development.
• NGA-Mn acts on the bacterial cell membrane via collective binding, disrupting vital functions.

Conclusions:

• NGA-Mn is a potent, broad-spectrum antibiotic with a novel mechanism of action.
• Single-atom engineering of materials like NGA-Mn offers a promising strategy for developing next-generation antibiotics.
• NGA-Mn presents a potential solution for overcoming antibiotic resistance while maintaining high cytocompatibility.