Experimental study on the influence of low-frequency and low-intensity ultrasound on the permeability of the Mycobacterium smegmatis cytoderm and potentiation with levofloxacin

Abstract

Tuberculosis is an infectious disease caused by the bacterium M. tuberculosis. The aim of this study was to investigate the bactericidal effect and underlying mechanisms of low-frequency and low-intensity ultrasound combined with levofloxacin treatment against M. smegmatis (a surrogate of M. tuberculosis). As part of this study, M. smegmatis was continuously irradiated with low frequency ultrasound (42kHz) using several different doses whereby both intensity (0.138, 0.190 and 0.329W/cm) and exposure time (5, 15 and 20min) were varied. Flow cytometric analyses revealed that the permeability of M. smegmatis increased following ultrasound exposure. The survival rate, structure and morphology of bacteria in the lower-dose (I=0.138W/cm for 5min) ultrasound group displayed no significant differences upon comparison with the untreated group. However, the survival rate of bacteria was significantly reduced and the bacterial structure was damaged in the higher-dose (I=0.329W/cm for 20min) ultrasound group. Ultrasound irradiation (0.138W/cm) was subsequently applied to M. smegmatis in combination with levofloxacin treatment for 5min. The results demonstrated that the bactericidal effect of ultrasonic irradiation combined with levofloxacin is higher compared to ultrasound alone or levofloxacin alone.

Synergistic Antifungal Effect of Amphotericin B-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles and Ultrasound against Candida albicans Biofilms

“…The use of low-frequency ultrasound (20 to 100 kHz) as a noninvasive treatment has been shown to improve cell membrane permeability, increase drug penetration, and achieve synergistic antibacterial effects by previous research (27)(28)(29). In the in vitro experiments, we demonstrated a highly effective synergistic antifungal effect of lowfrequency ultrasound combined with drug-loaded nanoparticles against C. albicans biofilms through XTT reduction assays and CLSM observation.…”

Low‐Frequency Ultrasound Enhances Bactericidal Activity of Antimicrobial Agents against Klebsiella pneumoniae Biofilm

“…Currently, most studies suggest that cavitation is the main responsible cause for the synergistic e ect. Liquid medium can form microbubbles, which may act on bio lms and increase its permeability to antimicrobial agents or even kill bacteria in bio lm [22][23][24]. However, for K. pneumoniae, many studies have demonstrated that the limited penetration of antibiotic molecules through the bio lm matrix is not the main reason for the increased resistance, but rather, the slow growth rate in the center of bio lm is [1].…”

Multiple Low Frequency Ultrasound Enhances Bactericidal Activity of Vancomycin against Methicillin-ResistantStaphylococcus aureusBiofilms

“…The exact mechanism of synergy is unclear. Several studies suggested that LFU cavitation was mainly responsible for the synergistic antimicrobial effect [ 14 – 16 ]. Under LFU treatment, liquid medium could form microbubbles, which might act on biofilms and increase its permeability to antimicrobial agents or even kill bacteria in biofilm.…”

“…Meanwhile, with more oxygen and nutrition entering biofilms, the susceptibility of MRSA or MSSA to antimicrobial agents may be reversed [ 18 ]. Other studies indicated that synergy may also be associated with heating or other mechanisms [ 16 , 19 ]. Overall, LFU possibly acts on the extracellular matrix of bacterial biofilm through multiple paths to facilitate the quick entrance of antimicrobial agents into biofilm.…”