Aminoglycoside antibiotics aggregate to form starch-like fibers on negatively charged surfaces and on phage lambda-DNA.
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.
Freie Universität Berlin, FB Biologie, Chemie, Pharmazie, Institut für Chemie/ Organische Chemie Takustr. 3, D-14195 Berlin, Germany.
Marta
M
Kopaczynska
Matthias
M
Lauer
Andrea
A
Schulz
Tianyu
T
Wang
Andreas
A
Schaefer
Jürgen-Hinrich
JH
Fuhrhop
D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D010582:Bacteriophage lambda / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004279:DNA, Viral / Q000737:chemistry*; D005374:Filtration; D007612:Kanamycin / Q000737:chemistry; D008969:Molecular Sequence Data; D009355:Neomycin / Q000737:chemistry; D010316:Particle Size; D055672:Static Electricity; D013499:Surface Properties; D014031:Tobramycin / Q000737:chemistry
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004279:DNA, Viral; D007612:Kanamycin; D009355:Neomycin; D014031:Tobramycin