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Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes
Published on: March 2, 2020
Zinc(II) coordination complexes as membrane-active fluorescent probes and antibiotics
Kristy M DiVittorio1, W Matthew Leevy, Edward J O'Neil
1Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, USA.
Chembiochem : a European Journal of Chemical Biology
|December 14, 2007
Summary
New zinc coordination complexes act as molecular probes, targeting bacterial membranes. A hydrophilic complex shows potent activity against antibiotic-resistant Staphylococcus aureus by depolarizing its cell membrane.
Area of Science:
- Coordination Chemistry
- Biomaterials Science
- Microbiology
Background:
- Zinc(II) coordination complexes with dipicolylamine can interact with biomembranes containing anionic phospholipids.
- Developing targeted molecular probes for biological applications is an ongoing area of research.
Purpose of the Study:
- To synthesize and characterize novel zinc coordination complexes with a 2,6-bis(zinc(II)-dipicolylamine)phenoxide core.
- To evaluate the membrane interaction, transport capabilities, and biological activity of these new complexes.
Main Methods:
- Synthesis of novel zinc coordination complexes.
- Liposome-based assays to study membrane partitioning and ion/phospholipid transport.
- Cytotoxicity assays on mammalian cells (LD50 determination).
- Antimicrobial susceptibility testing against Staphylococcus aureus, including antibiotic-resistant strains (MIC determination).
- Bacterial membrane depolarization assays.
- Fluorescence microscopy for bacterial imaging.
Main Results:
- Lipophilic analogues partitioned into zwitterionic and anionic vesicles, inducing phospholipid and carboxyfluorescein transport.
- Lipophilic complexes exhibited moderate mammalian cell toxicity.
- A hydrophilic analogue showed no mammalian cell toxicity (LD50 >50 microg mL(-1)) but potent activity against Staphylococcus aureus (MIC = 1 microg mL(-1)).
- This activity extended to vancomycin- and oxacillin-resistant strains, attributed to bacterial membrane depolarization.
- A fluorescent conjugate effectively stained bacteria, indicating potential for imaging.
Conclusions:
- The novel zinc coordination complexes demonstrate versatile properties, acting as membrane-targeting agents and potential antimicrobial agents.
- The hydrophilic analogue represents a promising lead for developing new antibiotics against resistant bacterial infections.
- The fluorescent capabilities suggest their utility as molecular probes for bacterial detection and imaging.
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