Chiral Nanoclusters as Alternative Therapeutic Strategies to Confront the Health Threat from Antibiotic-Resistant Pathogens.
Zhe WangYijin TianJinghua HaoYa LiuJie TangZhenlan XuYin LiuBiao TangXiu HuangNali ZhuZhigang LiLi-Gang HuLingxiangyu LiYawei WangGui-Bin JiangPublished in: ACS nano (2024)
Pseudomonas aeruginosa ( P. aeruginosa ), a drug-resistant Gram-negative pathogen, is listed among the "critical" group of pathogens by the World Health Organization urgently needing efficacious antibiotics in the clinics. Nanomaterials especially silver nanoparticles (AgNPs) due to the broad-spectrum antimicrobial activity are tested in antimicrobial therapeutic applications. Pathogens rapidly develop resistance to AgNPs; however, the health threat from antibiotic-resistant pathogens remains challenging. Here we present a strategy to prevent bacterial resistance to silver nanomaterials through imparting chirality to silver nanoclusters (AgNCs). Nonchiral AgNCs with high efficacy against P. aeruginosa causes heritable resistance, as indicated by a 5.4-fold increase in the minimum inhibitory concentration (MIC) after 9 repeated passages. Whole-genome sequencing identifies a Rhs mutation related to the wall of Gram-negative bacteria that possibly causes morphology changes in resistance compared to susceptible P. aeruginosa . Nevertheless, AgNCs with laevorotary chirality (l-AgNCs) induce negligible resistance even after 40 repeated passages and maintain a superior antibacterial efficiency at the MIC. l-AgNCs also show high cytocompatibility; negligible cytotoxicity to mammalian cells including JB6, H460, HEK293, and RAW264.7 is observed even at 30-fold MIC. l-AgNCs thus are examined as an alternative to levofloxacin in vivo, healing wound infections of P. aeruginosa efficaciously. This work provides a potential opportunity to confront the rising threat of antimicrobial resistance by developing chiral nanoclusters.
Keyphrases
- silver nanoparticles
- gram negative
- multidrug resistant
- antimicrobial resistance
- drug resistant
- pseudomonas aeruginosa
- acinetobacter baumannii
- healthcare
- public health
- gold nanoparticles
- mental health
- sensitive detection
- staphylococcus aureus
- health information
- primary care
- cystic fibrosis
- genome wide
- mass spectrometry
- biofilm formation
- label free
- escherichia coli
- wound healing
- dna methylation