Investigation of the mechanism of the bioacoustic effect.
Bacterial biofilms growing on implanted medical devices are difficult to eradicate, even with aggressive antibiotic therapy. However, application of ultrasound enhances the effectiveness of the antibiotic. The possible mechanisms of this phenomenon were explored in light of the observed influence of various ultrasonic parameters on the enhanced action of gentamicin against biofilms of Pseudomonas aeruginosa. It is postulated that ultrasound increases the transport of gentamicin through the cell membranes, which is the proposed rate determining step in killing by gentamicin. It is possible that the ultrasound perturbs the cell membrane and stimulates active uptake or permits passive uptake by temporarily disrupting the membrane or other structural cell components. The cell membrane disruption could be caused by high pressure, high shear stress, or cavitation. The dependence upon peak power density suggests that acoustic pressure plays a significant role. There is also a strong frequency component that causes the killing effect to decrease as frequency increases. A mathematical analysis of oscillatory shear stress on the cell shows that the magnitude of stress increases with frequency; thus, the hypothesis of oscillatory shear inducing antibiotic uptake is discounted. In addition, the shear displacement caused by shear forces is very small, so the shear disruption caused by oscillatory flow in an acoustic field has minimal impact. The experimental data also rule out the existence of transient cavitation in the bioacoustic effect. It is possible that stable cavitation and the accompanying microstreaming contribute to the bioacoustic effect.
Department of Chemical Engineering, Brigham Young University, Provo, Utah 84602, USA.
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D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism; D005839:Gentamicins / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D016459:Prosthesis-Related Infections / Q000188:drug therapy / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D014465:Ultrasonics
D000900:Anti-Bacterial Agents; D005839:Gentamicins