Sublethal vancomycin-induced ROS mediating antibiotic resistance in Staphylococcus aureus.

Gui-Qiu Li,Ting Qu,Feng Quan,Lan-Ying Cui,Yong-Chen Wang,Da-Wen Guo,Juan Lu,Shu-Lan Chen

doi:10.1042/bsr20140167

Abstract

Staphylococcus aureus is the leading cause of many human infectious diseases. Besides infectious dangers, S. aureus is well-known for the quickly developed drug resistance. Although great efforts have been made, mechanisms underlying the antibiotic effects of S. aureus are still not well clarified. Recently, reports have shown that oxidative stress connects with bactericidal antibiotics [Dwyer et al. (2009) Curr. Opin. Microbiol. 12: , 482-489]. Based on this point, we demonstrate that reactive oxygen species (ROS) induced by sublethal vancomycin may be partly responsible for the antibiotic resistance in heterogeneous vancomycin resistant S. aureus (hVRSA). Sublethal vancomycin treatment may induce protective ROS productions in hVRSA, whereas reduction in ROS level in hVRSA strains may increase their vancomycin susceptibility. Moreover, low dose of ROS in VSSA (vancomycin susceptible S. aureus) strains may promote their survival under vancomycin conditions. Our findings reveal that modest ROS generation may be protective for vancomycin resistance in hVRSA. These results recover novel insights into the relationship between oxidative stress and bacterial resistance, which has important applications for further use of antibiotics and development of therapeutics strategies for hVRSA.

Highlights

Staphylococcus aureus, a Gram-positive cocci, is one of the most common causes of nosocomial infections, from skin and chronic bone infections to devastating septicaemia and endocarditis [1]
To investigate the mechanism of how heterogeneous vancomycin resistant S. aureus (hVRSA) strains resists vancomycin and the role of reactive oxygen species (ROS) production in this process, we examined the survival of two vancomycin susceptible S. aureus (VSSA) and two hVRSA strains by gradient of vancomycin treatment
Growth conditions and viability assays hVRSA and VSSA strains were obtained from the first Affiliated Hospital of Harbin Medical University and their vancomycin resistance status was determined by the originating laboratory and confirmed by minimum inhibitory concentration (MIC) testhVRSA strains resist to vancomycin-mediated bacterial killing To compare the vancomycin susceptibility in hVRSA and VSSA strains, we examined the survival rate of S. aureus by different concentrations and times of vancomycin treatment

Summary

INTRODUCTION

Staphylococcus aureus, a Gram-positive cocci, is one of the most common causes of nosocomial infections, from skin and chronic bone infections to devastating septicaemia and endocarditis [1]. It seems likely that the thickening of cell wall is closely associated with vancomycin resistance in hVRSA strains [11,12]. To investigate the mechanism of how hVRSA strains resists vancomycin and the role of ROS production in this process, we examined the survival of two vancomycin susceptible S. aureus (VSSA) and two hVRSA strains by gradient of vancomycin treatment. We found that hVRSA strains are not susceptible to sublethal vancomycin treatment, which was accompanied by ROS productions. Our results exhibit that at least induced ROS may be beneficial to vancomycin resistance in two strains of hVRSA. To determine the cell viability of hVRSA and VSSA strains, overnight cultures (16 h) were diluted by 100 times and grown aerobically in LB at 37 ◦C to an A600 of 0.3. Quantitative data were shown as x +− s using ANOVA tests for comparisons

RESULTS

Findings

DISCUSSION