Small molecule-capped gold nanoparticles as potent antibacterial agents that target Gram-negative bacteria.
This report illustrates a new strategy in designing antibacterial agents--a series of commercially available compounds, amino-substituted pyrimidines (themselves completely inactive as antibiotics), when presented on gold nanoparticles (NPs), show antibacterial activities against multidrug-resistant clinical isolates, without external sources of energy such as IR. These pyrimidine-capped gold NPs exert their antibiotic actions via sequestration of magnesium or calcium ions to disrupt the bacterial cell membrane, resulting in leakage of cytoplasmic contents including nucleic acids from compromised cell membranes, and via interaction with DNA and inhibition of protein synthesis by internalized NPs. These amino-substituted pyrimidine-capped gold NPs induce bacterial resistance more slowly compared with conventional, small-molecule antibiotics and appear harmless to human cells; these NPs may hence be useful for clinical applications.
Zhao
Yuyun
Y
CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety, National Center for NanoScience and Technology, 11 Beiyitiao, ZhongGuanCun, Beijing, China 100190.
Tian
Yue
Y
Cui
Yan
Y
Liu
Wenwen
W
Ma
Wanshun
W
Jiang
Xingyu
X
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000166:cytology / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D011743:Pyrimidines / Q000737:chemistry; D013499:Surface Properties
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D050607:Organogold Compounds; D011743:Pyrimidines; D006046:Gold; C030986:pyrimidine