期刊
ACS INFECTIOUS DISEASES
卷 7, 期 4, 页码 721-732出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.0c00805
关键词
Gram-negative bacteria; drug resistance; antibiotic potentiator; antibiotic adjuvant; antimicrobial peptides; multivalent
资金
- National Institute of Allergy and Infectious Diseases [R01 AI132413]
- National Institutes of Health Pathway to Independence Award [K99 EB028311]
Researchers have successfully improved the intracellular delivery of antibiotics to Gram-negative pathogens by engineering macromolecular potentiators WD40, which reduced the minimum inhibitory concentrations of drugs, especially for antibiotics with hydrophobic and highly three-dimensional structures.
The drug-impermeable bacterial membrane in Gram-negative pathogens limits antibiotic access to intracellular drug targets. To expand our rapidly waning antibiotic arsenal, one approach is to improve the intracellular delivery of drugs with historically poor accumulation in Gram-negative bacteria. To do so, we engineered macromolecular potentiators to permeabilize the Gram-negative membrane to facilitate drug influx. Potentiators, known as WD40, were synthesized by grafting multiple copies of a cationic a-helical antimicrobial peptide, WLBU2, onto a dextran polymer scaffold. WD40 enabled drug uptake in the model pathogen P. aeruginosa, a capability that was not observed with unmodified WLBU2 peptide. WD40 was able to reduce minimum inhibitory concentrations of a drug panel by up to 3 orders of magnitude. Hydrophobic and highly three-dimensional antibiotics exhibited the greatest potentiation. Antibiotic activity was potentiated in several clinical strains and resulted in sensitization of drug-resistant strains to rifampin, a drug not previously used for Gram-negative infections.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据