Journal Article

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

Qu, Di, Chen, Junwen, Wu, Yang, Deng, Qiwen, Xiong, Yanpeng, Zheng, Jinxin, Yu, Zhijian, Zhao, Yuxi, Chen, Zhong, Tang, Yuanyuan

2022

Overview

Background Previous 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. Results The 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). Conclusion These 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Ampicillin / Ampicillin - pharmacology / Anti-Bacterial Agents - chemistry / Anti-Bacterial Agents - pharmacology / Anti-biofilm / Antibacterial / Antibiotics / Antimicrobial agents / Bacteria / Bactericidal activity / Binding sites / Biofilm formation / Biofilms / Biofilms - drug effects / Biofilms - growth & development / Biological Microscopy / Biomedical and Life Sciences / Chemical properties / Clinical isolates / Daptomycin / Daptomycin - pharmacology / Drug resistance / Drug Synergism / Drug therapy / E coli / Enterococcal infections / Enterococcus faecium / Enterococcus faecium - drug effects / Enterococcus faecium - enzymology / Enterococcus faecium - growth & development / Gram-positive bacteria / Gram-Positive Bacterial Infections - microbiology / Heterocyclic compounds / Histidine / Histidine kinase / Histidine Kinase - antagonists & inhibitors / Histidine Kinase - metabolism / Humans / Kinases / Laser microscopy / Lasers / Life Sciences / Microbial Sensitivity Tests / Microbiology / Minimum inhibitory concentration / Multidrug resistant organisms / Mycology / Nosocomial infections / Parasitology / Pathogens / Penicillin / Phosphorylation / Physiological aspects / Planktonic cells / Polystyrene / Polystyrene resins / Proteins / Recombinant Proteins - metabolism / Staphylococcus infections / Testing / Thiazoles - chemistry / Thiazoles - pharmacology / Urinary tract diseases / Urinary tract infections / Urogenital system / Virology / Virulence