Radezolid Is More Effective Than Linezolid Against Planktonic Cells and Inhibits Enterococcus faecalis Biofilm Formation

Abstract

The aim of this study was to compare the effects of radezolid and linezolid on planktonic and biofilm cells of Enterococcus faecalis. A total of 302 E. faecalis clinical isolates were collected, and the minimum inhibitory concentrations (MICs) of radezolid and linezolid were determined by the agar dilution method. Changes in the transcriptome of a highlevel, in vitro-induced linezolid-resistant isolate were assessed by RNA sequencing and RT-qPCR, and the roles of efflux pump-related genes were confirmed by overexpression analysis. Biofilm biomass was evaluated by crystal violet staining and the adherent cells in the biofilms were quantified according to CFU numbers. The MIC 50 /MIC 90 values of radezolid (0.25/0.50 mg/L) against the 302 E. faecalis clinical isolates were eightfold lower than those of linezolid (2/4 mg/L). The radezolid MICs against the highlevel linezolid-resistant isolates (linezolid MICs ≥ 64 mg/L) increased to ≥ 4 mg/L with mutations in the four copies of the V domain of the 23S rRNA gene. The mRNA expression level of OG1RF_12220 (mdlB2, multidrug ABC superfamily ATP-binding cassette transporter) increased in the high-level linezolid-resistant isolates, and radezolid and linezolid MICs against the linezolid-sensitive isolate increased with overexpression of OG1RF_12220. Radezolid (at 1/4 or 1/8× the MIC) inhibited E. faecalis biofilm formation to a greater extent than linezolid, which was primarily achieved through the inhibition of ahrC, esp, relA, and relQ transcription in E. faecalis. In conclusion, radezolid is more effective than linezolid against planktonic E. faecalis cells and inhibits biofilm formation by this bacterium.

Comparison of Anti-Microbic and Anti-Biofilm Activity Among Tedizolid and Radezolid Against Linezolid-Resistant Enterococcus faecalis Isolates

“…The efflux pump may be involved in the resistance to tedizolid and radezolid for E. faecalis isolates. However, we analyzed the effects of linezolid, tedizolid, and radzolide on the expression of efflux pump gene ( OG1RF12220, OG1RF10126 , and OG1RF1049 ) referring to Zheng et al, 26 our results showed it did not influence these efflux pumps. The role of other efflux pump would also be studied in our future studies.…”

“…The expression levels of E. faecalis (FC2234 FC2559 FC1728 FC1037 FC2398 FC2471) efflux pump-related genes ( OG1RF12220, OG1RF10126 , and OG1RF10495 ) were determined by RT-qPCR based on published reports. 26 Real-time qPCR was performed using the 7500 RTPCR System (Thermo Fisher Scientific, Marsiling, Singapore) equipped with the SYBRTM Green RT-PCR Kit (TOYOBO, Osaka, Japan). The primers used for qRT-PCR are listed in Table S1 .…”

“… 25 Besides, previous research has reported that the MICs for linezolid or radezolid showed a 2 to 8 fold decreased by the presence of PAβN (efflux pump inhibitors). 26 Although tedizolid and radezolid belong to the same oxazolidinones class drugs, the differences in their antimicrobial activity against linezolid-resistant E. faecalis are still unclear. Moreover, the variable effect of tedizolid and radezolid on the biofilm of linezolid-resistant E. faecalis compared with linezolid and the role and differences of efflux pump in these three generations oxazolidinones resistance is still largely unknown.…”

Strategies to Improve the Potency of Oxazolidinones towards Bacterial Biofilms

“…[144][145] In a recent study, Qu and colleagues investigated the effect of radezolid on planktonic and biofilm cells of Enterococcus faecalis and compared the results with linezolid. [146] The authors found a significantly greater effect of radezolid on planktonic E. faecalis cells than linezolid. The biofilm biomass was evaluated by crystal violet staining and the adherent cells were quantified according to CFU numbers.…”

A Recent Overview of 1,2,3-Triazole-Containing Hybrids as Novel Antifungal Agents: Focusing on Synthesis, Mechanism of Action, and Structure-Activity Relationship (SAR)

“…e antibiotics Tazobactam/Ceftolozane [29], Radezolid [30], Cefatrizine [31], Tertbutyldimethylsilylspiroaminooxathioledioxide (TSAO) [32], and the Carboxyamidotriazole (CAI) [33] are examples of pharmaceutical drugs containing 1,2,3-triazoles scaffold (Scheme 9). We discuss the synthesis process of these pharmaceutical medicines in this study.…”