The synergistic bactericidal effect of vancomycin on UTMD treated biofilm involves damage to bacterial cells and enhancement of metabolic activities

Jian Hu,Ying Li,Yanfen Ma,Ning Zhang,Qian Wu,Lifang Li,Nianan He,Chedong Zhao,Xiaoqin Wang

doi:10.1038/s41598-017-18496-3

Abstract

In this study, the synergistic effect of vancomycin, a cell wall synthesis inhibitor, and ultrasound-targeted microbubble destruction (UTMD), on cell viability of Staphylococcus epidermidis, embedded in biofilm, was investigated. Biofilms are the leading causes of antibiotic-resistant bacterial infections of medical implants and prosthetics worldwide. The antibiotic-resistant nature of biofilm-embedded pathogens poses a critical challenge to the medical community. Previously, studies have demonstrated the efficacy of using ultrasound waves and UTMD in circumventing this problem. However, the mechanism(s) underlying this phenomenon was not clear. Here, the present study showed that both ultrasound and UTMD damaged the cell wall structure of S. epidermidis, and floccules and fragments from damaged cells were observed on transmission electron microscope micrograph. However, the cell membrane integrity was not seriously affected by treatments, and the treatment increased the metabolic activity levels of the dormant biofilm-embedded bacteria, detected by confocal laser scanning microscope and flow cytometry, which could make them susceptible to the effect of the antibiotic. Thus, the biological mechanism underlying the efficacy of the combined treatment involving UTMD and vancomycin in the case of S. epidermidis biofilm was dissected, which may be utilized for further investigations on other biofilm pathogens before clinical use.

Highlights

IntroductionMedical implant-related infections have emerged as challenging problems with the extensive use of medical implants and prosthetics (such as prosthetic valve, artificial catheter, intravascular stent, bone prosthesis, etc.) in clinical approaches
In recent years, medical implant-related infections have emerged as challenging problems with the extensive use of medical implants and prosthetics in clinical approaches
Biofilms lead to the development of antibiotic-resistant infections in medical implants and prosthetics, which renders the treatment of such infections challenging

Summary

Introduction

Medical implant-related infections have emerged as challenging problems with the extensive use of medical implants and prosthetics (such as prosthetic valve, artificial catheter, intravascular stent, bone prosthesis, etc.) in clinical approaches. Studies showed that low energy ultrasound has similar biological effects on bacteria, i.e., it improves the lethal effect of antibiotics on drug-resistant bacteria or biofilms[14,15,16,17,18,19]. Whether ultrasound or UTMD can directly affect the physiological state of bacteria in biofilm and reduce its drug resistance is still under investigation. We used the biofilm of Staphylococcus epidermidis as a model, and explored the biological effect of ultrasound or UTMD on bacterial survival in biofilms to provide a theoretical basis for the use of ultrasound or UTMD in improving the efficacy of antibiotic treatment on implanted prosthetic-related biofilm infections

Methods

Results

Conclusion