In vitro activities of thiazolidione derivatives combined with daptomycin against clinical Enterococcus faecium strains

BMC Microbiology

Yuanyuan Tang¹  Qiwen Deng¹  Yuxi Zhao¹  Junwen Chen¹  Yanpeng Xiong¹  Jinxin Zheng¹  Zhijian Yu¹  Zhong Chen²  Yang Wu³  Di Qu³ 

[1] Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, 518052, Shenzhen, China;Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, 518052, Shenzhen, China;Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Medical Microbiology and Parasitology, School of Basic Medical Science and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, 200032, Shanghai, China;Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Medical Microbiology and Parasitology, School of Basic Medical Science and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, 200032, Shanghai, China;

关键词: Enterococcus faecium;    Antibacterial;    Anti-biofilm;    Biofilm formation;   

DOI  :  10.1186/s12866-021-02423-8

来源: Springer

【 摘 要 】

BackgroundPrevious reports have demonstrated two thiazolidione derivatives (H2-60 and H2-81) can robustly inhibit the planktonic growth and biofilm formation of S. epidermidis and S. aureus by targeting the histidine kinase YycG. Whereas the antibacterial and anti-biofilm activity of these two thiazolidione derivatives (H2-60 and H2-81) against Enterococcus faecium remains elusive. Here, the pET28a-YycG recombinant plasmid were in vitro expressed in E. coli competent cell BL21 (DE3) and induced to express YycG’ protein (conding HisKA and HATPase_c domain) by 0.5 mM IPTG and was purified by Ni – NTA agarose and then for the autophosphorylation test. Antimicrobial testing and time-killing assay were also be determined. Anti-biofilm activity of two derivatives with sub-MIC concentration towards positive biofilm producers of clinical E. faecium were detected using polystyrene microtiter plate and CLSM.ResultsThe MICs of H2-60 and H2-81 in the clinical isolates of E. faecium were in the range from 3.125 mg/L to 25 mg/L. Moreover, either H2-60 or H2-81 showed the excellent bactericidal activity against E. faecium with monotherapy or its combination with daptomycin by time-killing assay. E. faecium planktonic cells can be decreased by H2-60 or H2-81 for more than 3 × log10 CFU/mL after 24 h treatment when combined with daptomycin. Furthermore, over 90% of E. faecium biofilm formation could markedly be inhibited by H2-60 and H2-81 at 1/4 × MIC value. In addition, the frequency of the eradicated viable cells embedded in mature biofilm were evaluated by the confocal laser microscopy, suggesting that of H2-60 combined with ampicillin or daptomycin was significantly high when compared with single treatment (78.17 and 74.48% vs. 41.59%, respectively, P < 0.01).ConclusionThese two thiazolidione derivatives (H2-60 and H2-81) could directly impact the kinase phosphoration activity of YycG of E. faecium. H2-60 combined with daptomycin exhibit the excellent antibacterial and anti-biofilm activity against E. faecium by targeting YycG.

【 授权许可】

CC BY