Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious nosocomial infections, and recurrent MRSA infections primarily result from the survival of persister cells after antibiotic treatment. Gas plasma, a novel source of ROS (reactive oxygen species) and RNS (reactive nitrogen species) generation, not only inactivates pathogenic microbes but also restore the sensitivity of MRSA to antibiotics. This study further found that sublethal treatment of MRSA with both plasma and plasma-activated saline increased the antibiotic sensitivity and promoted the eradication of persister cells by tetracycline, gentamycin, clindamycin, chloramphenicol, ciprofloxacin, rifampicin, and vancomycin. The short-lived ROS and RNS generated by plasma played a primary role in the process and induced the increase of many species of ROS and RNS in MRSA cells. Thus, our data indicated that the plasma treatment could promote the effects of many different classes of antibiotics and act as an antibiotic sensitizer for the treatment of antibiotic-resistant bacteria involved in infectious diseases.

Highlights

  • Antibiotics are the primary treatment for infectious bacterial diseases (Li et al, 2017)

  • Electron spin resonance (ESR) spectroscopy was used for the measurement of short-lived species, in which the results were the concentrations of spin adducts, only reflecting the relative concentrations of the specific reactive oxygen species (ROS) and/or RNS

  • We demonstrated that treating Methicillin-resistant Staphylococcus aureus (MRSA) sublethally with plasma-generated ROS and RNS decreased the minimal inhibitory concentration (MIC) of several antibiotics and increased persister eradication, along with increases in the levels of ROS and RNS in MRSA cells

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Summary

Introduction

Antibiotics are the primary treatment for infectious bacterial diseases (Li et al, 2017). Infections with multidrug-resistant bacteria are occurring more frequently, and few or no drugs are available to combat them (Boucher et al, 2009; Wright, 2016; Gonzalez-Bello, 2017). One of the major multidrug-resistant bacteria is methicillin-resistant Staphylococcus aureus (MRSA), which is recognized as a leading cause of nosocomial infections (Shahsavan et al, 2012; Emaneini et al, 2017). Persisters are a small non-growing population of bacteria which could escape from different antibiotics (Levin and Rozen, 2006). Persisters extend the duration of antibiotic treatment, cause the recurrence of infectious diseases, and the generation and ascent of antibiotic resistance (Levin and Rozen, 2006).

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