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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02453

Synergistic microbicidal effect of auranofin and antibiotics against planktonic and biofilm-encased S. aureus and E. faecalis

  • 1Third Xiangya Hospital, Central South University, China

Methicillin-resistant/susceptible Staphylococcus aureus (MRSA/MSSA) and Enterococcus faecalis strains are often found in community- and hospital-acquired infections. The single use of conventional antibiotics hardly completely kills the bacterial cells of interest, especially in the form of biofilms. Thus, drug repurposing and antimicrobial combination are promising ways to solve this problem. Antimicrobial susceptibility assays against cocci in a suspension and in a biofilm mode of growth were performed with broth microdilution methods. Checkerboard assays and the cutaneous mouse infection model were used to examine the activity of auranofin and conventional antibiotics alone and in combination. In the present study, auranofin possesses potent antimicrobial activities against both planktonic cells and biofilms with minimum inhibitory concentrations ranging 0.125-0.5 mg/L. Auranofin in combination with linezolid or fosfomycin showed synergistic antimicrobial activities against S. aureus MSSA and MRSA both in vitro and in vivo. Similarly, auranofin also behaved synergistic effect with chloramphenicol against E. faecalis. Additionally, auranofin improved the antibiofilm efficacy of chloramphenicol and linezolid, even on the biofilms grown on a catheter surface. Though, S. epidermidis showed significant susceptibility to AF treatment, no synergistic antimicrobial effects were observed with antibiotics we tested. In all, the use of a combination of auranofin with linezolid, fosfomycin and chloramphenicol can provide a synergistic microbicidal effect in vitro and in vivo, which rapidly enhances antimicrobial activity and may help prevent or delay the emergence of resistance.

Keywords: Auranofin, Biofilm, combination therapy, Subcutaneous abscess model, Staphylococcus aureus, Enterococcus faecalis

Received: 12 Jul 2019; Accepted: 11 Oct 2019.

Copyright: © 2019 She, Zhou, Li, Liu, Xu, Chen, Luo and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yong Wu, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China, wuyong_zn@csu.edu.cn