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Synergistic Microbicidal Effect of Auranofin and Antibiotics Against Planktonic and Biofilm-Encased S. aureus and E. faecalis.

ABSTRACT: 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.

SUBMITTER: She P

PROVIDER: S-EPMC6821689 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Like many bacteria, Enterococcus faecalis encodes a number of adhesins involved in colonization or infection of different niches. Two well-studied E. faecalis adhesins, aggregation substance (AS) and endocarditis- and biofilm-associated pili (Ebp), both contribute to biofilm formation on abiotic surfaces and in endocarditis, suggesting that they may be expressed at the same time. Because different regulatory pathways have been reported for AS and Ebp, here, we examined if they are coexpressed on the same cells and what is the functional impact of coexpression on individual cells and within a population. We found that while Ebp are only expressed on a subset of cells, when Ebp and AS are expressed on the same cells, pili interfere with AS-mediated clumping and impede AS-mediated conjugative plasmid transfer during planktonic growth. However, when the population density increases, horizontal gene transfer rates normalize and are no longer affected by pilus expression. Instead, at higher cell densities during biofilm formation, Ebp and AS differentially contribute to biofilm development and structure, synergizing to promote maximal biofilm formation.IMPORTANCE Most bacteria express multiple adhesins that contribute to surface attachment and colonization. However, the network and relationships between the various adhesins of a single bacterial species are less well understood. Here, we examined two well-characterized adhesins in Enterococcus faecalis, aggregation substance and endocarditis- and biofilm-associated pili, and found that they exhibit distinct functional contributions depending on the growth stage of the bacterial community. Pili interfere with aggregation substance-mediated clumping and plasmid transfer under planktonic conditions, whereas the two adhesins structurally complement one another during biofilm development. This study advances our understanding of how E. faecalis, a ubiquitous member of the human gut microbiome and an opportunistic pathogen, uses multiple surface structures to evolve and thrive.

Dataset Information

Synergistic Microbicidal Effect of Auranofin and Antibiotics Against Planktonic and Biofilm-Encased S. aureus and E. faecalis.

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