Aminoglycoside antibiotics aggregate to form starch-like fibers on negatively charged surfaces and on phage
Marta Kopaczynska1, Matthias Lauer, Andrea Schulz
1Freie Universität Berlin, FB Biologie, Chemie, Pharmazie, Institut für Chemie/ Organische Chemie Takustr. 3, D-14195 Berlin, Germany.
Abstract:
The water-soluble (> 200 mg/mL) antibiotics tobramycin, kanamycin, and neomycin spontaneously produce rigid fibers on negatively charged surfaces (mica, graphite, DNA). Atomic force microscopy showed single strands of tobramycin on mica at pH 7 with a length of several hundred nanometers and a diameter of 0.5 nm and double helices with a diameter of 1.0 nm and a helical pitch of 7 nm. At pH 13 (NaOH) up to 15 microm long, rigid fibers with a uniform height of 2.4 nm and an apparent helical pitch of 30 nm were formed along the sodium silicate channels on the surface of mica. Kanamycin and neomycin behaved similarly. Fibers of similar length and width, but without secondary structure, were obtained from aqueous solutions at pH 7 on amorphous, hydrophilized carbon and characterized by transmission electron microscopy. Overstretched phage lambda-DNA strands with a height of 1.0 nm on mica did not interact with tobramycin coils at pH 7. After treatment with EDTA, however, the height of the magnesium-free lambda-DNA strands grew from 1.0 to 3.8 nm after treatment with tobramycin, which suggests a wrapping by the supramolecular fibers. Such fibers may interact with F-actin fibers in biological cells, which would explain the known aggressiveness of aminoglycosides toward bacterial cell membranes and their ototoxicity.
Insights
Aminoglycoside antibiotics like tobramycin form rigid fibers on surfaces. These supramolecular fibers may interact with biological structures, explaining antibiotic toxicity.
Area of Science:
- Biochemistry
- Materials Science
- Microbiology
Background:
- Aminoglycoside antibiotics (tobramycin, kanamycin, neomycin) are water-soluble and widely used.
- Their interaction with biological structures at a molecular level is not fully understood.
- Spontaneous fiber formation by these antibiotics has not been previously reported.
Purpose of the Study:
- To investigate the self-assembly and structural properties of aminoglycoside antibiotics.
- To explore the potential interactions of these antibiotic-formed fibers with biological molecules.
- To elucidate the mechanism behind aminoglycoside-induced toxicity.
Main Methods:
- Atomic Force Microscopy (AFM) to visualize fiber morphology and dimensions on mica surfaces at different pH levels.
- Transmission Electron Microscopy (TEM) for characterization of fibers on amorphous carbon.
- Interaction studies with lambda-DNA strands before and after EDTA treatment.
Main Results:
- Tobramycin, kanamycin, and neomycin spontaneously form rigid fibers on negatively charged surfaces.
- AFM revealed single strands (0.5 nm diameter) and double helices (1.0 nm diameter, 7 nm pitch) of tobramycin at pH 7.
- At pH 13, longer fibers (up to 15 µm) with distinct helical structures (2.4 nm height, 30 nm pitch) were observed.
- TEM confirmed similar fibers without secondary structure on carbon surfaces.
- Tobramycin fibers wrapped magnesium-free lambda-DNA strands, increasing their height from 1.0 to 3.8 nm.
Conclusions:
- Water-soluble aminoglycoside antibiotics self-assemble into supramolecular fibers with distinct secondary structures.
- These fibers demonstrate an ability to interact with and potentially wrap DNA.
- The findings suggest a potential mechanism for aminoglycoside toxicity involving interactions with cellular components like F-actin.
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